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Valachis A, Karihtala P, Geisler J, Tuxen MK. Metastatic triple-negative breast cancer - current treatment strategies in the Nordics: a modified Delphi study. Acta Oncol 2025; 64:349-357. [PMID: 40045533 PMCID: PMC11898304 DOI: 10.2340/1651-226x.2025.42733] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2024] [Accepted: 02/19/2025] [Indexed: 03/09/2025]
Abstract
BACKGROUND AND PURPOSE This study aimed to assess current treatment strategies for metastatic triple-negative breast cancer (mTNBC) and the perceptions of clinical experts in Sweden, Denmark, Norway, Finland, and Iceland, comparing them to international guidelines to provide insights into how these therapies are implemented and adapted to national Nordic guidelines. METHODS A three-round modified Delphi method was followed with consensus defined as 70% agreement. A steering committee selected 20 experienced oncologists as panellists and developed the questionnaires. Questions included items related to treatment preferences in different treatment lines with different clinical scenarios in mTNBC patients. RESULTS In the first round, eight out of 33 questions on clinical treatment reached consensus with 14 out of 27 in the second round reaching consensus. In round three, eight out of eight questions reached consensus. The preferred treatment for mTNBC patients with PD-L1 positive was checkpoint inhibitors (CPI) in combination with chemotherapy. For patients with germline BRCA mutation and PD-L1 negative disease, PARP-inhibitors were preferred as 1L and sacituzumab govitecan (SG) in both 2L and later lines. Disagreement was observed for chemotherapy in later lines where evidence is sparse or lacking. INTERPRETATION The high level of consensus for new treatment strategies, such as CPI and PARP-inhibitors in 1L and SG in 2L or later lines, in comparison with the limited consensus for older treatments, such as chemotherapy, may reflect the growing academic evidence for different treatment strategies. Understanding the treatment patterns across different countries contributes to gaining consensus on the upcoming therapeutic advances.
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Affiliation(s)
- Antonis Valachis
- Department of Oncology, Faculty of Medicine and Health, Örebro University, Örebro, Örebro, Sweden.
| | - Peeter Karihtala
- Department of Oncology, Helsinki University Hospital Comprehensive Cancer Centre and University of Helsinki, Helsinki, Finland
| | - Jürgen Geisler
- Department of Oncology, Division of Medicine, Akershus University Hospital (AHUS), Lørenskog, Norway & Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Campus AHUS, Norway
| | - Malgorzata K Tuxen
- Department of Oncology, Herlev and Gentofte University Hospital, Herlev, Denmark
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García-Saenz JÁ, Rodríguez-Lescure Á, Cruz J, Albanell J, Alba E, Llombart A. Second-Line Treatment Options for Patients with Metastatic Triple-Negative Breast Cancer: A Review of the Clinical Evidence. Target Oncol 2025; 20:191-213. [PMID: 39806129 PMCID: PMC11933194 DOI: 10.1007/s11523-024-01125-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/21/2024] [Indexed: 01/16/2025]
Abstract
Metastatic triple-negative breast cancer has a poor prognosis and poses significant therapeutic challenges. Until recently, limited therapeutic options have been available for patients with advanced disease after failure of first-line chemotherapy. The aim of this review is to assess the current evidence supporting second-line treatment options in patients with metastatic triple-negative breast cancer. Evidence was reviewed from controlled clinical trials in which eribulin, vinorelbine, capecitabine, gemcitabine, gemcitabine plus carboplatin, fam-trastuzumab-deruxtecan, sacituzumab govitecan, olaparib, and talazoparib were used in the second-line treatment for metastatic breast cancer, either as study drugs or as comparators. The benefit of treatment was evaluated using the European Society for Medical Oncology-Magnitude of Clinical Benefit Scale. Based on the evidence review, sacituzumab govitecan was identified as the preferred second-line treatment option for patients with metastatic triple-negative breast cancer, supported by clinical evidence and consensus across international clinical guidelines. Olaparib and talazoparib are of use in patients with human epidermal growth factor receptor 2-negative metastatic breast cancer and germline BRCA1/2 mutations. Exploratory data for fam-trastuzumab-deruxtecan suggest a survival benefit in human epidermal growth factor receptor 2-low, hormone-receptor-negative patients, but further solid evidence is required. Other chemotherapies with lower European Society for Medical Oncology-Magnitude of Clinical Benefit Scale scores may continue to be useful in highly selected patients.
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Affiliation(s)
- José Ángel García-Saenz
- Instituto de Investigación Sanitaria Hospital Clínico San Carlos, IdISSC, Calle Profesor Martín Lagos, S/N, 28040, Madrid, Spain.
| | | | - Josefina Cruz
- Hospital Universitario de Canarias, Santa Cruz de Tenerife, Spain
| | - Joan Albanell
- Hospital del Mar Research Institute, Barcelona, Spain
- Pompeu Fabra University, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Oncología, CIBERONC-ISCIII, Madrid, Spain
| | - Emilio Alba
- Medical Oncology Unit, Universitary Hospital Virgen de la Victoria, CIBERONC, IBIMA, Malaga, Spain
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3
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Bardia A, Jhaveri K, Im SA, Pernas S, De Laurentiis M, Wang S, Martínez Jañez N, Borges G, Cescon DW, Hattori M, Lu YS, Hamilton E, Zhang Q, Tsurutani J, Kalinsky K, Rubini Liedke PE, Xu L, Fairhurst RM, Khan S, Denduluri N, Rugo HS, Xu B, Pistilli B. Datopotamab Deruxtecan Versus Chemotherapy in Previously Treated Inoperable/Metastatic Hormone Receptor-Positive Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer: Primary Results From TROPION-Breast01. J Clin Oncol 2025; 43:285-296. [PMID: 39265124 PMCID: PMC11771365 DOI: 10.1200/jco.24.00920] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2024] [Revised: 05/27/2024] [Accepted: 07/30/2024] [Indexed: 09/14/2024] Open
Abstract
PURPOSE The global, phase 3, open-label, randomized TROPION-Breast01 study assessed the trophoblast cell surface antigen 2-directed antibody-drug conjugate datopotamab deruxtecan (Dato-DXd) versus investigator's choice of chemotherapy (ICC) in hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer. METHODS Adult patients with inoperable/metastatic HR+/HER2‒ breast cancer, who had disease progression on endocrine therapy, for whom endocrine therapy was unsuitable, and had received one to two previous lines of chemotherapy in the inoperable/metastatic setting, were randomly assigned 1:1 to Dato-DXd (6 mg/kg once every 3 weeks) or ICC (eribulin/vinorelbine/capecitabine/gemcitabine). Dual primary end points were progression-free survival (PFS) by blinded independent central review (BICR) and overall survival (OS). RESULTS Patients were randomly assigned to Dato-DXd (n = 365) or ICC (n = 367). Dato-DXd significantly reduced the risk of progression or death versus ICC (PFS by BICR hazard ratio [HR], 0.63 [95% CI, 0.52 to 0.76]; P < .0001). Consistent PFS benefit was observed across subgroups. Although OS data were not mature, a trend favoring Dato-DXd was observed (HR, 0.84 [95% CI, 0.62 to 1.14]). The rate of grade ≥3 treatment-related adverse events (TRAEs) with Dato-DXd was lower than ICC (20.8% v 44.7%). The most common TRAEs (any grade; grade ≥3) were nausea (51.1%; 1.4%) and stomatitis (50%; 6.4%) with Dato-DXd and neutropenia (grouped term, 42.5%; 30.8%) with ICC. CONCLUSION Patients receiving Dato-DXd had statistically significant and clinically meaningful improvement in PFS and a favorable and manageable safety profile, compared with ICC. Results support Dato-DXd as a novel treatment option for patients with inoperable/metastatic HR+/HER2‒ breast cancer who have received one to two previous lines of chemotherapy in this setting.
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Affiliation(s)
- Aditya Bardia
- Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA
- Massachusetts General Hospital Cancer Center, Boston, MA
| | - Komal Jhaveri
- Memorial Sloan Kettering Cancer Center, New York, NY
- Weill Cornell Medical College, New York, NY
| | - Seock-Ah Im
- Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul National University, Seoul, Republic of Korea
| | - Sonia Pernas
- Institut Català d'Oncologia-IDIBELL, L'Hospitalet, Barcelona, Spain
| | | | - Shusen Wang
- Cancer Center of Sun Yat-sen University, Guangzhou, China
| | - Noelia Martínez Jañez
- Ramón y Cajal University Hospital, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain
| | | | | | | | - Yen-Shen Lu
- National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
| | | | - Qingyuan Zhang
- Harbin Medical University Cancer Hospital, Harbin, China
| | - Junji Tsurutani
- Advanced Cancer Translational Research Institute, Showa University, Tokyo, Japan
| | - Kevin Kalinsky
- Winship Cancer Institute at Emory University, Atlanta, GA
| | - Pedro Emanuel Rubini Liedke
- Hospital das Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil
- UPCO—Pesquisa Clinica em Oncologia, Porto Alegre, Brazil
- Oncoclinicas Porto Alegre, Porto Alegre, Brazil
| | - Lu Xu
- AstraZeneca, Gaithersburg, MD
| | | | | | | | - Hope S. Rugo
- University of California San Francisco Comprehensive Cancer Center, San Francisco, CA
| | - Binghe Xu
- National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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4
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Fan Y, Zhang Q, Yan M, Qu X, Yin Y, Sun T, Yang J, Wang Y, Wang X, Niu Z, Wang X, Sun S, Zhao W, Liu Y, Niu M, Zhao X, Xu B. Intravenous liposomal irinotecan in metastatic triple-negative breast cancer after ≥ 2 prior lines of chemotherapy: a phase Ib study. Nat Commun 2025; 16:3. [PMID: 39746964 PMCID: PMC11696226 DOI: 10.1038/s41467-024-55090-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2024] [Accepted: 12/01/2024] [Indexed: 01/04/2025] Open
Abstract
This study (NCT04728035) aimed to explore the safety and efficacy of liposomal irinotecan (HE072) in patients with metastatic triple-negative breast cancer (mTNBC). This study consisted of two parts. In part 1, the 3 + 3 design was used to investigate three dose levels of HE072 (50, 70 and 90 mg/m2). In part 2, patients were enrolled in two cohorts (mTNBC and HER2-negative breast cancer brain metastasis [BCBM]), and received HE072 70 mg/m2 every two weeks (Q2W). The primary endpoints were maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D), and treatment emergent adverse events (TEAEs). The secondary endpoints were pharmacokinetic profiles and efficacy including objective response rate (ORR) and disease control rate (DCR) (all patients) and Central Nervous System ORR and clinical benefit rate (CBR, for patients with HER2-negative BCBM), duration of response, progression free survival (PFS), overall survival (OS). A total of 119 patients were enrolled, including 101 mTNBC and 18 HER2-negative BCBM. One dose limiting toxicity (grade 3 nausea and vomiting) occurred at 70 mg/m2, and the MTD was not reached. The most common ≥ grade 3 TEAEs related to HE072 included neutropenia (21.0%), leukopenia (18.5%), diarrhea (10.1%). Among 87 evaluable patients with mTNBC, 22 patients (25.3%) achieved overall response. The DCR was 67.8% (59/87). The median PFS and OS were 4.8 months and 14.1 months, respectively. The RP2D was 70 mg/m2 Q2W. Promising antitumor activity in heavily pre-treated patients with mTNBC was observed, which warrants further validation.
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Affiliation(s)
- Ying Fan
- National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Qingyuan Zhang
- Harbin Medical University Affiliated Cancer Hospital, Harbin, China
| | - Min Yan
- Henan Cancer Hospital, Zhengzhou, China
| | - Xiujuan Qu
- The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Yongmei Yin
- Jiangsu Provincial People's Hospital, Nanjing, China
| | - Tao Sun
- Liaoning Cancer Hospital, Shenyang, China
| | - Jin Yang
- The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Ying Wang
- Sun Yat Sen Memorial Hospital of Sun Yat Sen University, Guangzhou, China
| | - Xu Wang
- Tianjin Cancer Hospital, Tianjin, China
| | | | - Xinshuai Wang
- The First Affiliated Hospital of Henan University of Science and Technology, Zhengzhou, China
| | | | - Weihong Zhao
- Chinese People's Liberation Army General Hospital, Beijing, China
| | - Yanping Liu
- CSPC Zhongqi Pharmaceutical Technology (Shijiazhuang) Co., Ltd, Shijiazhuang, China
| | - Miao Niu
- CSPC Zhongqi Pharmaceutical Technology (Shijiazhuang) Co., Ltd, Shijiazhuang, China
| | - Xuemin Zhao
- CSPC Zhongqi Pharmaceutical Technology (Shijiazhuang) Co., Ltd, Shijiazhuang, China
| | - Binghe Xu
- National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
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Ni M, Zhou L, Lu Y, Guo D, Li X, Li L, Zhang L, Chen M, Zhang L, Xu F, Yuan Z, Wang S, Shi Y, Yang A, An X. Eribulin plus carboplatin combination for HER2-negative metastatic breast cancer: a multicenter, real-world cohort study. BMC Cancer 2024; 24:1214. [PMID: 39350055 PMCID: PMC11443731 DOI: 10.1186/s12885-024-12953-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2024] [Accepted: 09/13/2024] [Indexed: 10/04/2024] Open
Abstract
BACKGROUND Pre-clinical data suggests a potential synergistic effect of eribulin and platinum. However, clinical data on the combination for metastatic breast cancer (mBC) is lacking. We evaluated the efficacy and safety of eribulin plus carboplatin (ErCb) in patients with mBC. PATIENTS AND METHODS This multicenter, real-world cohort study included patients with pre-treated metastatic triple negative breast cancer (TNBC) or endocrine-refractory hormone receptor (HR) positive, HER2-negative mBC who received ErCb. Eribulin (1.4 mg/m2) and carboplatin (target AUC = 2) were administered intravenously on day 1 and 8 of 21-day cycle. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were evaluated. RESULTS From March 2022 to December 2023, a cohort of 37 patients were recruited to the study. Among them, 22 patients have TNBC and 15 have HR + HER2 - mBC. Of the 22 patients with TNBC, 8 had an initial diagnosis of the HR + HER2 - subtype. The median treatment was 6 cycles (range, 2 - 8 cycles). In the full cohort, TNBC, and HR + HER2 - subgroup, the ORR were 51.4%, 54.5% and 46.7%, the DCR were 81.1%, 81.8% and 80%, and the median PFS were 5 months, 5 months, and 5.2 months, respectively. The median OS was 12.7 months in the entire cohort and 12.8 months in TNBC subgroup. The most common grade 3/4 hematological AEs were neutropenia (37.8%), leukopenia (35.1%), febrile neutropenia (10.8%), thrombocytopenia (5.4%), and anemia (2.7%). No grade 3/4 non-hematological AEs were observed. CONCLUSION ErCb demonstrated favorable efficacy and tolerability in patients with heavily pre-treated mBC, especially TNBC. The findings of the current study warrant further investigation of the application of this combination in earlier lines of mBC treatment.
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Affiliation(s)
- Mengqian Ni
- Department of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, No. 651, Dongfeng Road East, Yuexiu District, Guangzhou, 510060, China
| | - Lijia Zhou
- Department of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, No. 651, Dongfeng Road East, Yuexiu District, Guangzhou, 510060, China
| | - Yongkui Lu
- Affiliated Cancer Hospital of Guangxi Medical University, Nanning, 530021, China
| | - Dachuan Guo
- Department of Minimally Invasive Interventional Therapy, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China
| | - Xiuyue Li
- Central Hospital of Pan-Yu, Guangzhou, 511486, China
| | - Lixia Li
- Cancer Hospital, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524000, China
| | - Lidong Zhang
- Puning People's Hospital, Jieyang, Guangdong, 515300, China
| | - Meiting Chen
- Department of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, No. 651, Dongfeng Road East, Yuexiu District, Guangzhou, 510060, China
| | - Lulu Zhang
- Department of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, No. 651, Dongfeng Road East, Yuexiu District, Guangzhou, 510060, China
| | - Fei Xu
- Department of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, No. 651, Dongfeng Road East, Yuexiu District, Guangzhou, 510060, China
| | - Zhongyu Yuan
- Department of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, No. 651, Dongfeng Road East, Yuexiu District, Guangzhou, 510060, China
| | - Shusen Wang
- Department of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, No. 651, Dongfeng Road East, Yuexiu District, Guangzhou, 510060, China
| | - Yanxia Shi
- Department of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, No. 651, Dongfeng Road East, Yuexiu District, Guangzhou, 510060, China.
| | - Anli Yang
- Department of Breast Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, No. 651, Dongfeng Road East, Yuexiu District, Guangzhou, 510060, China.
| | - Xin An
- Department of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, No. 651, Dongfeng Road East, Yuexiu District, Guangzhou, 510060, China.
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Pinto A, Guarini C, Giampaglia M, Sanna V, Melaccio A, Lanotte L, Santoro AN, Pini F, Cusmai A, Giuliani F, Gadaleta-Caldarola G, Fedele P. Synergizing Immunotherapy and Antibody-Drug Conjugates: New Horizons in Breast Cancer Therapy. Pharmaceutics 2024; 16:1146. [PMID: 39339183 PMCID: PMC11435286 DOI: 10.3390/pharmaceutics16091146] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2024] [Revised: 08/23/2024] [Accepted: 08/26/2024] [Indexed: 09/30/2024] Open
Abstract
The advent of immunotherapy and antibody-drug conjugates (ADCs) have revolutionized breast cancer treatment, offering new hope to patients. However, challenges, such as resistance and limited efficacy in certain cases, remain. Recently, the combination of these therapies has emerged as a promising approach to address these challenges. ADCs play a crucial role by delivering cytotoxic agents directly to breast cancer cells, minimizing damage to healthy tissue and enhancing the tumor-killing effect. Concurrently, immunotherapies harness the body's immune system to recognize and eliminate cancer cells. This integration offers potential to overcome resistance mechanisms and significantly improve therapeutic outcomes. This review explores the rationale behind combining immunotherapies with ADCs, recent advances in this field, and the potential implications for breast cancer treatment.
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Affiliation(s)
- Antonello Pinto
- Oncology Unit, "Dario Camberlingo" Hospital, 72021 Francavilla Fontana, Italy
| | - Chiara Guarini
- Oncology Unit, "Dario Camberlingo" Hospital, 72021 Francavilla Fontana, Italy
| | | | - Valeria Sanna
- Oncology Unit, "Ospedale Civile Santissima Annunziata" Hospital, 07100 Sassari, Italy
| | | | - Laura Lanotte
- Oncology Unit, "Mons. Dimiccoli" Hospital, 70051 Barletta, Italy
| | | | - Francesca Pini
- Oncology Unit, "Dario Camberlingo" Hospital, 72021 Francavilla Fontana, Italy
| | - Antonio Cusmai
- "Don Tonino Bello", I.R.C.C.S. Istituto Tumori "Giovanni Paolo II", 70124 Bari, Italy
| | | | | | - Palma Fedele
- Oncology Unit, "Dario Camberlingo" Hospital, 72021 Francavilla Fontana, Italy
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Oey O, Wijaya W, Redfern A. Eribulin in breast cancer: Current insights and therapeutic perspectives. World J Exp Med 2024; 14:92558. [PMID: 38948420 PMCID: PMC11212747 DOI: 10.5493/wjem.v14.i2.92558] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Revised: 02/21/2024] [Accepted: 03/20/2024] [Indexed: 06/19/2024] Open
Abstract
Eribulin is a non-taxane synthetic analogue approved in many countries as third-line treatment for the treatment of patients with metastatic breast cancer. In addition to its mitotic property, eribulin has non-mitotic properties including but not limited to, its ability to induce phenotypic reversal of epithelial to mesenchymal transition, vascular remodelling, reduction in immunosuppressive tumour microenvironment. Since approval, there has been a surge in studies investigating the application of eribulin as an earlier-line treatment and also in combination with other agents such as immunotherapy and targeted therapy across all breast cancer sub-types, including hormone receptor positive, HER2 positive and triple negative breast cancer, many demonstrating promising activity. This review will focus on the application of eribulin in the treatment of metastatic breast cancer across all subtypes including its role as an earlier-line agent, its toxicity profile, and potential future directions.
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Affiliation(s)
- Oliver Oey
- Faculty of Medicine, University of Western Australia, Nedlands 6009, Australia
- Department of Medical Oncology, Sir Charles Gairdner Hospital, Nedlands 6009, WA, Australia
| | - Wynne Wijaya
- Department of Oncology, University of Oxford, Oxford OX3 7DQ, United Kingdom
- Department of Internal Medicine, Universitas Gadjah Mada, Sleman 55281, Indonesia
| | - Andrew Redfern
- Department of Medical Oncology, Fiona Stanley Hospital, Murdoch 6150, WA, Australia
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8
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Hurvitz SA, Bardia A, Punie K, Kalinsky K, Carey LA, Rugo HS, Diéras V, Phan S, Delaney R, Zhu Y, Tolaney SM. Subgroup analyses from the phase 3 ASCENT study of sacituzumab govitecan in metastatic triple-negative breast cancer. NPJ Breast Cancer 2024; 10:33. [PMID: 38664404 PMCID: PMC11045722 DOI: 10.1038/s41523-024-00635-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Accepted: 03/28/2024] [Indexed: 04/28/2024] Open
Abstract
In this post hoc analysis of the ASCENT study, we compared outcomes with sacituzumab govitecan (SG) vs single-agent chemotherapy in clinically important subgroups of patients with metastatic triple-negative breast cancer (mTNBC). Patients with mTNBC refractory to/relapsing after ≥2 prior chemotherapies (≥1 in the metastatic setting) were randomized 1:1 to receive SG or treatment of physician's choice (TPC) until unacceptable toxicity/progression. The primary endpoint was progression-free survival (PFS) per RECIST 1.1 by central review in patients without brain metastases. Patients with brain metastases were allowed if metastases were stable ≥4 weeks. In the intention-to-treat (ITT) population, 19% of patients were age ≥65 years; 12% were Black, and 12% had brain metastases. SG improved PFS and overall survival (OS), respectively, vs TPC in patients age ≥65 years (7.1 vs 2.4 months and 14.7 vs 8.9 months), or of Black race (5.4 vs 2.2 months and 13.8 vs 8.5 months), consistent with outcomes in the ITT population. Patients with brain metastases had numerically higher median PFS with SG vs TPC, but median OS was similar between treatment groups. SG was well tolerated and had a manageable safety profile consistent with the full safety population across all subgroups; neutropenia and diarrhea were the most common treatment-emergent adverse events. These findings confirm the meaningful clinical benefit of SG vs standard chemotherapy in patient subgroups with high unmet needs. SG should be considered an effective and safe treatment option for patients with mTNBC eligible for second-line or later therapy. ClinicalTrials.gov Number: NCT02574455.
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Affiliation(s)
- Sara A Hurvitz
- Clinical Research Division, Department of Medicine, UW Medicine, Fred Hutchinson Cancer Center, Seattle, WA, USA.
| | - Aditya Bardia
- Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA
| | - Kevin Punie
- Department of General Medical Oncology and Multidisciplinary Breast Centre, Leuven Cancer Institute and University Hospitals Leuven, Leuven, Belgium
| | - Kevin Kalinsky
- Winship Cancer Institute, Emory University, Atlanta, GA, USA
| | - Lisa A Carey
- University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC, USA
| | - Hope S Rugo
- University of California San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA
| | | | - See Phan
- Gilead Sciences Inc., Foster City, CA, USA
| | | | - Yanni Zhu
- Gilead Sciences Inc., Foster City, CA, USA
| | - Sara M Tolaney
- Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
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9
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Giulietti M, Piva F, Cecati M, Maggio S, Guescini M, Saladino T, Scortichini L, Crocetti S, Caramanti M, Battelli N, Romagnoli E. Effects of Eribulin on the RNA Content of Extracellular Vesicles Released by Metastatic Breast Cancer Cells. Cells 2024; 13:479. [PMID: 38534323 PMCID: PMC10969587 DOI: 10.3390/cells13060479] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2023] [Revised: 02/23/2024] [Accepted: 03/04/2024] [Indexed: 03/28/2024] Open
Abstract
Extracellular vesicles (EVs) are small lipid particles secreted by almost all human cells into the extracellular space. They perform the essential function of cell-to-cell communication, and their role in promoting breast cancer progression has been well demonstrated. It is known that EVs released by triple-negative and highly aggressive MDA-MB-231 breast cancer cells treated with paclitaxel, a microtubule-targeting agent (MTA), promoted chemoresistance in EV-recipient cells. Here, we studied the RNA content of EVs produced by the same MDA-MB-231 breast cancer cells treated with another MTA, eribulin mesylate. In particular, we analyzed the expression of different RNA species, including mRNAs, lncRNAs, miRNAs, snoRNAs, piRNAs and tRNA fragments by RNA-seq. Then, we performed differential expression analysis, weighted gene co-expression network analysis (WGCNA), functional enrichment analysis, and miRNA-target identification. Our findings demonstrate the possible involvement of EVs from eribulin-treated cells in the spread of chemoresistance, prompting the design of strategies that selectively target tumor EVs.
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Affiliation(s)
- Matteo Giulietti
- Department of Specialistic Clinical and Odontostomatological Sciences, Polytechnic University of Marche, 60131 Ancona, Italy
| | - Francesco Piva
- Department of Specialistic Clinical and Odontostomatological Sciences, Polytechnic University of Marche, 60131 Ancona, Italy
| | - Monia Cecati
- Department of Specialistic Clinical and Odontostomatological Sciences, Polytechnic University of Marche, 60131 Ancona, Italy
| | - Serena Maggio
- Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy
| | - Michele Guescini
- Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy
| | - Tiziana Saladino
- Oncology Unit AST3, Macerata Hospital, Via Santa Lucia 2, 62100 Macerata, Italy
| | - Laura Scortichini
- Oncology Unit AST3, Macerata Hospital, Via Santa Lucia 2, 62100 Macerata, Italy
| | - Sonia Crocetti
- Oncology Unit AST3, Macerata Hospital, Via Santa Lucia 2, 62100 Macerata, Italy
| | - Miriam Caramanti
- Oncology Unit AST3, Macerata Hospital, Via Santa Lucia 2, 62100 Macerata, Italy
| | - Nicola Battelli
- Oncology Unit AST3, Macerata Hospital, Via Santa Lucia 2, 62100 Macerata, Italy
| | - Emanuela Romagnoli
- Oncology Unit AST3, Macerata Hospital, Via Santa Lucia 2, 62100 Macerata, Italy
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10
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Bardia A, Jhaveri K, Kalinsky K, Pernas S, Tsurutani J, Xu B, Hamilton E, Im SA, Nowecki Z, Sohn J, Laurentiis MD, Jañez NM, Adamo B, Lee KS, Jung KH, Rubovszky G, Tseng LM, Lu YS, Yuan Y, Maxwell MJ, Haddad V, Khan SS, Rugo HS, Pistilli B. TROPION-Breast01: Datopotamab deruxtecan vs chemotherapy in pre-treated inoperable or metastatic HR+/HER2- breast cancer. Future Oncol 2024; 20:423-436. [PMID: 37387213 DOI: 10.2217/fon-2023-0188] [Citation(s) in RCA: 20] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/01/2023] Open
Abstract
Improving the prognosis for patients with metastatic HR+/HER2- breast cancer remains an unmet need. Patients with tumors that have progressed on endocrine therapy and/or are not eligible for endocrine therapy had limited treatment options beyond chemotherapy. Antibody-drug conjugates are a novel and promising treatment class in this setting. Datopotamab deruxtecan (Dato-DXd) consists of a TROP2-directed humanized IgG1 monoclonal antibody attached via a serum-stable cleavable linker to a topoisomerase I inhibitor payload. TROPION-Breast01 is an ongoing phase III study that is evaluating the efficacy and safety of Dato-DXd compared with investigator's choice of standard-of-care chemotherapy in patients with inoperable or metastatic HR+/HER2- breast cancer who have received one or two prior lines of systemic chemotherapy in the inoperable or metastatic setting. Clinical Trial Registration: NCT05104866 (ClinicalTrials.gov).
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Affiliation(s)
- Aditya Bardia
- Massachusetts General Hospital Cancer Center, Boston, MA, USA
| | - Komal Jhaveri
- Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Weill Cornell Medical College, New York, NY, USA
| | - Kevin Kalinsky
- Winship Cancer Institute at Emory University, Atlanta, GA, USA
| | - Sonia Pernas
- Institut Català d'Oncologia, IDIBELL, L'Hospitalet, Barcelona, Spain
| | | | - Binghe Xu
- National Cancer Center / National Clinical Research Center for Cancer / Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Erika Hamilton
- Sarah Cannon Research Institute / Tennessee Oncology, Nashville, TN, USA
| | - Seock-Ah Im
- Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul National University, Seoul, Republic of Korea
| | - Zbigniew Nowecki
- Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland
| | - Joohyuk Sohn
- Yonsei University College of Medicine, Seoul, Republic of Korea
| | | | - Noelia Martínez Jañez
- Ramón y Cajal University Hospital, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain
| | - Barbara Adamo
- August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Hospital Clinic, University of Barcelona, Barcelona, Spain
| | - Keun Seok Lee
- Center for Breast Cancer, National Cancer Center, Goyang, Republic of Korea
| | - Kyung Hae Jung
- Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | | | - Ling-Ming Tseng
- Comprehensive Breast Health Center, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Yen-Shen Lu
- National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Yuan Yuan
- Formerly City of Hope Comprehensive Cancer Center, Duarte, CA, USA; Currently: Cedars-Sinai Cancer Center, Los Angeles, CA, USA
| | | | | | | | - Hope S Rugo
- University of California San Francisco Comprehensive Cancer Center, San Francisco, CA, USA
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11
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Wu Q, Xu L. Challenges in HER2-low breast cancer identification, detection, and treatment. TRANSLATIONAL BREAST CANCER RESEARCH : A JOURNAL FOCUSING ON TRANSLATIONAL RESEARCH IN BREAST CANCER 2024; 5:3. [PMID: 38751682 PMCID: PMC11093058 DOI: 10.21037/tbcr-23-48] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/22/2023] [Accepted: 11/27/2023] [Indexed: 05/18/2024]
Abstract
Recently, human epidermal growth factor receptor 2 (HER2)-low breast cancer (BC) has emerged as a novel subset within the category of HER2-negative BC, prompting a reassessment of the immunohistochemical negative scores of 0, 1+, and the 2+/in situ hybridization (ISH) negative phenotype. Recent clinical trials have provided compelling evidence of the substantial clinical advantages offered by novel antibody-drug conjugates (ADCs) that target HER2 in the treatment of these specific tumor cohorts. Notably, trastuzumab deruxtecan (T-Dxd), an ADC that specifically targets HER2, has recently received approval from the US Food and Drug Administration as the inaugural targeted therapeutic option for HER2-low BC. However, the classification of HER2-low BC as a distinct subtype, the methods for detecting HER2-low BC, and the optimal treatment approach for HER2-low BC remain subjects of ongoing debate and lack consensus. This comprehensive review aims to address these pertinent concerns, offering insights into the nuanced tumor biology underlying HER2-low BC and critically analyzing the current treatment pathways available. By synthesizing available evidence, the objective is to contribute to an enhanced understanding of HER2-low BC, providing a foundation for more informed clinical decisions and further advancements in tailored therapeutic approaches. As the medical community navigates these uncertainties, this review seeks to consolidate existing knowledge, fostering a collective effort toward establishing consensus in the diagnosis and treatment of HER2-low BC.
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Affiliation(s)
- Qian Wu
- Thyroid and Breast Surgery, Peking University First Hospital, Beijing, China
| | - Ling Xu
- Thyroid and Breast Surgery, Peking University First Hospital, Beijing, China
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12
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Gumusay O, Huppert LA, Magbanua MJM, Wabl CA, Assefa M, Chien AJ, Melisko ME, Majure MC, Moasser M, Park J, Rugo HS. A phase Ib/II study of eribulin in combination with cyclophosphamide in patients with advanced breast cancer. Breast Cancer Res Treat 2024; 203:197-204. [PMID: 37815684 PMCID: PMC10787873 DOI: 10.1007/s10549-023-07073-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2023] [Accepted: 08/06/2023] [Indexed: 10/11/2023]
Abstract
PURPOSE We hypothesized that eribulin combined with cyclophosphamide (EC) would be an effective combination with tolerable toxicity for the treatment of advanced breast cancer (ABC). METHODS Patients with histologically confirmed metastatic or unresectable ABC with any number of prior lines of therapy were eligible to enroll. In the dose escalation cohort, dose level 0 was defined as eribulin 1.1 mg/m2 and cyclophosphamide 600 mg/m2, and dose level 1 was defined as eribulin 1.4 mg/m2 and cyclophosphamide 600 mg/m2. Eribulin was given on days 1 and 8 and cyclophosphamide on day 1 of a 21-day cycle. In the dose expansion cohort, enrollment was expanded at dose level 1. The primary objective was clinical benefit rate (CBR), and secondary objectives were response rate (RR), duration of response (DOR), progression-free survival (PFS), and safety. RESULTS No dose-limiting toxicities were identified in the dose escalation cohort (n = 6). In the dose expansion cohort, an additional 38 patients were enrolled for a total of 44 patients, including 31 patients (70.4%) with hormone receptor-positive (HR +)/HER2- disease, 12 patients (27.3%) with triple-negative breast cancer (TNBC), and 1 patient (2.3%) with HR + /HER2 + disease. Patients had a median age of 56 years (range 33-82 years), 1 prior line of hormone therapy (range 0-6), and 2 prior lines of chemotherapy (range 0-7). CBR was 79.5% (35/44; 7 partial response, 28 stable disease) and the median DOR was 16.4 weeks (range 13.8-21.1 weeks). Median PFS was 16.4 weeks (95% CI: 13.8-21.1 weeks). The most common grade 3/4 adverse event was neutropenia (47.7%, n = 21). Fourteen of 26 patients (53.8%) with circulating tumor cell (CTC) data were CTC-positive ([Formula: see text] 5 CTC/7.5 mL) at baseline. Median PFS was shorter in patients who were CTC-positive vs. negative (13.1 vs 30.6 weeks, p = 0.011). CONCLUSION In heavily pretreated patients with ABC, treatment with EC resulted in an encouraging CBR of 79.5% and PFS of 16.4 weeks, which compares favorably to single-agent eribulin. Dose reduction and delays were primarily due to neutropenia. The contribution of cyclophosphamide to eribulin remains unclear but warrants further evaluation. NCT01554371.
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Affiliation(s)
- Ozge Gumusay
- Department of Medical Oncology, School of Medicine, Acibadem University, Istanbul, Turkey
| | - Laura A Huppert
- University of California San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA
| | | | - Chiara A Wabl
- University of California San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA
| | | | - Amy Jo Chien
- University of California San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA
| | - Michelle E Melisko
- University of California San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA
| | - Melanie C Majure
- University of California San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA
| | - Mark Moasser
- University of California San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA
| | - John Park
- University of California San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA
| | - Hope S Rugo
- University of California San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA.
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13
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Dent RA, Cescon DW, Bachelot T, Jung KH, Shao ZM, Saji S, Traina TA, Vukovic P, Mapiye D, Maxwell MJ, Schmid P, Cortés J. TROPION-Breast02: Datopotamab deruxtecan for locally recurrent inoperable or metastatic triple-negative breast cancer. Future Oncol 2023; 19:2349-2359. [PMID: 37526149 DOI: 10.2217/fon-2023-0228] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/02/2023] Open
Abstract
Despite recent treatment advances, the prognosis for patients with locally recurrent inoperable or metastatic triple-negative breast cancer (TNBC) remains poor. The antibody-drug conjugate datopotamab deruxtecan (Dato-DXd) is composed of a humanized anti-TROP2 IgG1 monoclonal antibody linked to a topoisomerase I inhibitor payload via a stable, cleavable linker. The phase III TROPION-Breast02 trial in patients previously untreated for locally recurrent inoperable or metastatic TNBC, who are not candidates for PD-1/PD-L1 inhibitors is evaluating efficacy and safety of Dato-DXd versus investigator's choice of chemotherapy (ICC). Approximately 600 patients will be randomized 1:1 to Dato-DXd 6 mg/kg iv. every 3 weeks or ICC (paclitaxel, nab-paclitaxel, carboplatin, capecitabine or eribulin mesylate). Dual primary end points are progression-free survival by blinded independent central review and overall survival.
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Affiliation(s)
| | - David W Cescon
- Princess Margaret Cancer Centre/UHN, Toronto, ON, Canada
| | | | - Kyung Hae Jung
- Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | | | | | | | | | | | | | | | - Javier Cortés
- International Breast Cancer Center, Pangaea Oncology IBCC, Barcelona, Spain
- Medica Scientia Innovation Research (MedSIR), Barcelona, Spain
- Universidad Europea de Madrid, Faculty of Biomedical & Health Sciences, Department of Medicine, Madrid, Spain
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14
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Xie J, Li S, Li Y, Li J. Cost-effectiveness of sacituzumab govitecan versus chemotherapy in patients with relapsed or refractory metastatic triple-negative breast cancer. BMC Health Serv Res 2023; 23:706. [PMID: 37386633 DOI: 10.1186/s12913-023-09728-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Accepted: 06/21/2023] [Indexed: 07/01/2023] Open
Abstract
BACKGROUND The effectiveness of sacituzumab govitecan for metastatic triple-negative breast cancer (TNBC) has been reported in recent research, however, the value of the effectiveness and cost of sacituzumab govitecan is still unclear. METHODS A microsimulation model was developed using data from the ASCENT trial to assess the cost-effectiveness of sacituzumab govitecan for patients with relapsed or refractory metastatic TNBC over a lifetime. Model inputs, including clinical data, patient characteristics, and direct medical costs, were based on the ASCENT trial, public databases, and published literature. The primary outcomes of the model were the incremental cost-effectiveness ratio (ICER) and quality-adjusted life-years (QALYs). Univariate and probabilistic sensitivity analysis (PSA) and multiple scenario analyses were performed to address the uncertainty of the model. RESULTS Our results revealed that sacituzumab govitecan versus chemotherapy costs $293,037 and yielded an additional 0.2340 of QALYs in the whole population with metastatic TNBC, leading to an ICER of $1,252,295 gained. And in the population with metastatic TNBC without brain metastasis, the sacituzumab govitecan versus chemotherapy costs $309,949 and obtained an extra 0.2633 of QALYs, which resulted in an ICER of $1,177,171/QALYs. Univariate analyses indicated that the model outcomes were most sensitive to the drug cost of sacituzumab govitecan, the utility of progression-free disease, and the utility of progressed disease. CONCLUSION From the US payer perspective, sacituzumab govitecan is unlikely to be a cost-effective option for patients with relapsed or refractory metastatic TNBC compared with chemotherapy. Based on the value standpoint, a price decrease of sacituzumab govitecan is expected to increase the cost-effectiveness of sacituzumab govitecan in patients with metastatic TNBC.
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Affiliation(s)
- Jiao Xie
- Department of Otolaryngology-Head and Neck Surgery, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China
- Clinical Nursing Teaching and Research Section, The Second Xiangya Hospital, Central South University, Changsha, 410011, China
| | - SiNi Li
- Clinical Nursing Teaching and Research Section, The Second Xiangya Hospital, Central South University, Changsha, 410011, China.
- The Nethersole School of Nursing, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong.
- Present Address: The Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan, China.
| | - YaMin Li
- Clinical Nursing Teaching and Research Section, The Second Xiangya Hospital, Central South University, Changsha, 410011, China
| | - JianHe Li
- Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, 410011, China
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15
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Wang J, Sun T, Ouyang Q, Han Y, Xu B. A phase Ib study of TQB2450 plus anlotinib in patients with advanced triple-negative breast cancer. iScience 2023; 26:106876. [PMID: 37275528 PMCID: PMC10238930 DOI: 10.1016/j.isci.2023.106876] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Revised: 03/22/2023] [Accepted: 05/10/2023] [Indexed: 06/07/2023] Open
Abstract
This study explored the safety and preliminary efficacy of the anti-PD-L1 antibody TQB2450 combined with the multi-kinase inhibitor anlotinib in advanced triple-negative breast cancer (TNBC). Patients with advanced TNBC who received at least one line of systemic therapy with anthracyclines and/or taxanes were enrolled in the dose-escalation and dose-expansion cohorts. Between May 29, 2019 and September 28, 2020, 34 patients were enrolled (three in the dose-escalation cohort and 31 in the dose-expansion cohort). The ORR was 26.5% (95% CI, 12.9-44.4) and the DCR was 73.5% (95% CI, 55.6-87.1). The median PFS was 5.6 (95% CI, 2.9-7.5) months, and the median OS was not reached. Seventeen (50.0%) patients had grade ≥3 treatment-related adverse events, with the most common being QT interval prolongation (17.6%) and hypertension (14.7%). No treatment-related deaths occurred. TQB2450 combined with anlotinib as a chemotherapy-free treatment shows promising efficacy with a manageable safety profile for patients with previously treated advanced TNBC.
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Affiliation(s)
- Jiayu Wang
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Tao Sun
- Liaoning Cancer Hospital & Institute, Shenyang, China
| | - Quchang Ouyang
- Department of Breast Cancer Medical Oncology, Hunan Cancer Hospital, Changsha, China
| | - Yiqun Han
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Binghe Xu
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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16
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Yang J, Han J, Zeng N, Yan X. Cost-effectiveness of trastuzumab deruxtecan in previously treated human epidermal growth factor receptor 2-low metastatic breast cancer. Ther Adv Med Oncol 2023; 15:17588359231169983. [PMID: 37228255 PMCID: PMC10204055 DOI: 10.1177/17588359231169983] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2022] [Accepted: 03/28/2023] [Indexed: 05/27/2023] Open
Abstract
Background Results from DESTINY-Breast04 trial revealed that trastuzumab deruxtecan (T-DXd) improved both progression-free survival and overall survival for patients with human epidermal growth factor receptor 2 (HER2)-low metastatic breast cancer (mBC). However, the economic impact of this practice remains unclear. The purpose of this study was to evaluate the cost-effectiveness of T-DXd on HER2-low mBC from the viewpoint of U.S. payers. Methods Using the clinical data from the DESTINY-Breast04 trial, a three-state Markov model was created to assess the economic and health effects of T-DXd versus chemotherapy. The incremental cost-effectiveness ratio (ICER) and willingness-to-pay threshold were determined and compared. One-way and probabilistic sensitivity analysis were used to measure parameter uncertainty. Results In the overall HER2-low population, T-DXd provided additional 0.47 quality-adjusted life-years (QALYs) at an increased cost of $149,222 compared with chemotherapy, yielding an ICER of $317,494/QALY. The ICER was $353,903/QALY in the hormone receptor (HR)-positive subgroup, which decreased to $259,825/QALY in the HR-negative subgroup. The sensitivity analysis found that T-DXd would not be cost-effective in the base-case. The expected cost of T-DXd will be less than $4,281/cycle ($11.33/mg) or $1,903/cycle ($5.03/mg) to achieve a 50 or 90% cost-benefit probability, respectively. Conclusions T-DXd provides significant health benefit for patients with HER2-low mBC compared with chemotherapy but is unlikely to be cost-effective in the United States.
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Affiliation(s)
| | | | - Ni Zeng
- Department of Head and Neck Oncology and
Department of Radiation Oncology, Cancer Center and State Key Laboratory of
Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, P. R.
China
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17
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Rugo HS, Bardia A, Marmé F, Cortes J, Schmid P, Loirat D, Trédan O, Ciruelos E, Dalenc F, Pardo PG, Jhaveri KL, Delaney R, Fu O, Lin L, Verret W, Tolaney SM. Sacituzumab Govitecan in Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer. J Clin Oncol 2022; 40:3365-3376. [PMID: 36027558 DOI: 10.1200/jco.22.01002] [Citation(s) in RCA: 154] [Impact Index Per Article: 51.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2022] [Revised: 06/15/2022] [Accepted: 07/28/2022] [Indexed: 11/20/2022] Open
Abstract
PURPOSE Hormone receptor-positive (HR+) human epidermal growth factor receptor 2-negative (HER2-) endocrine-resistant metastatic breast cancer is treated with sequential single-agent chemotherapy with poor outcomes. Sacituzumab govitecan (SG) is a first-in-class antibody-drug conjugate with an SN-38 payload targeting trophoblast cell-surface antigen 2, an epithelial antigen expressed in breast cancer. METHODS In this global, randomized, phase III study, SG was compared with physician's choice chemotherapy (eribulin, vinorelbine, capecitabine, or gemcitabine) in endocrine-resistant, chemotherapy-treated HR+/HER2- locally recurrent inoperable or metastatic breast cancer. The primary end point was progression-free survival (PFS) by blinded independent central review. RESULTS Patients were randomly assigned to receive SG (n = 272) or chemotherapy (n = 271). The median age was 56 years, 95% had visceral metastases, and 99% had a prior cyclin-dependent kinase 4/6 inhibitor, with three median lines of chemotherapy for advanced disease. Primary end point was met with a 34% reduction in risk of progression or death (hazard ratio, 0.66 [95% CI, 0.53 to 0.83; P = .0003]). The median PFS was 5.5 months (95% CI, 4.2 to 7.0) with SG and 4.0 months (95% CI, 3.1 to 4.4) with chemotherapy; the PFS at 6 and 12 months was 46% (95% CI, 39 to 53) v 30% (95% CI, 24 to 37) and 21% (95% CI, 15 to 28) v 7% (95% CI, 3 to 14), respectively. Median overall survival (first planned interim analysis) was not yet mature (hazard ratio, 0.84; P = .14). Key grade ≥ 3 treatment-related adverse events (SG v chemotherapy) were neutropenia (51% v 38%) and diarrhea (9% v 1%). CONCLUSION SG demonstrated statistically significant PFS benefit over chemotherapy, with a manageable safety profile in patients with heavily pretreated, endocrine-resistant HR+/HER2- advanced breast cancer and limited treatment options.
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Affiliation(s)
- Hope S Rugo
- Department of Medicine, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA
| | - Aditya Bardia
- Medical Oncology, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA
| | - Frederik Marmé
- Medical Faculty Mannheim, Heidelberg University, University Hospital Mannheim, Heidelberg, Germany
| | - Javier Cortes
- Medical Oncology Department, International Breast Cancer Center, Pangaea Oncology, Quironsalud Group, Madrid and Barcelona, Spain
- Faculty of Biomedical and Health Sciences, Department of Medicine, Universidad Europea de Madrid, Madrid, Spain
| | - Peter Schmid
- Barts Cancer Institute, Queen Mary University of London, London, United Kingdom
| | - Delphine Loirat
- Medical Oncology Department and D3i, Institut Curie, Paris, France
| | - Olivier Trédan
- Medical Oncology Department, Centre Léon Bérard, Lyon, France
| | - Eva Ciruelos
- Medical Oncology, Hospital Universitario 12 de Octubre, Madrid, Spain
| | | | | | | | - Rosemary Delaney
- Department of Clinical Development, Gilead Sciences Inc, Foster City, CA
| | - Olivia Fu
- Department of Global Patient Safety, Gilead Sciences Inc, Foster City, CA
| | - Lanjia Lin
- Department of Biostatistics, Gilead Sciences Inc, Foster City, CA
| | - Wendy Verret
- Department of Clinical Development, Gilead Sciences Inc, Foster City, CA
| | - Sara M Tolaney
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
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18
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Carey LA, Loirat D, Punie K, Bardia A, Diéras V, Dalenc F, Diamond JR, Fontaine C, Wang G, Rugo HS, Hurvitz SA, Kalinsky K, O'Shaughnessy J, Loibl S, Gianni L, Piccart M, Zhu Y, Delaney R, Phan S, Cortés J. Sacituzumab govitecan as second-line treatment for metastatic triple-negative breast cancer-phase 3 ASCENT study subanalysis. NPJ Breast Cancer 2022; 8:72. [PMID: 35680967 PMCID: PMC9184615 DOI: 10.1038/s41523-022-00439-5] [Citation(s) in RCA: 39] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2021] [Accepted: 05/04/2022] [Indexed: 11/08/2022] Open
Abstract
Patients with triple-negative breast cancer (TNBC) who relapse early after (neo)adjuvant chemotherapy have more aggressive disease. In the ASCENT trial, sacituzumab govitecan (SG), an antibody-drug conjugate composed of an anti-Trop-2 antibody coupled to SN-38 via a hydrolyzable linker, improved outcomes over single-agent chemotherapy of physician's choice (TPC) in metastatic TNBC (mTNBC). Of 468 patients without known baseline brain metastases, 33/235 vs 32/233 patients (both 14%) in the SG vs TPC arms, respectively, received one line of therapy in the metastatic setting and experienced disease recurrence ≤12 months after (neo)adjuvant chemotherapy. SG prolonged progression-free survival (median 5.7 vs 1.5 months [HR, 0.41; 95% CI, 0.22-0.76]) and overall survival (median 10.9 vs 4.9 months [HR, 0.51; 95% CI, 0.28-0.91]) vs TPC, with a manageable safety profile in this subgroup consistent with the overall population. In this second-line setting, as with later-line therapy, SG improved survival over conventional chemotherapy for patients with mTNBC.
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Affiliation(s)
- Lisa A Carey
- University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC, USA.
| | - Delphine Loirat
- Medical Oncology Department and D3i, Institut Curie, Paris, France
| | - Kevin Punie
- Department of General Medical Oncology and Multidisciplinary Breast Centre, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium
| | - Aditya Bardia
- Department of Hematology/Oncology, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA
| | - Véronique Diéras
- Department of Medical Oncology, Centre Eugène Marquis, Rennes, France
| | | | - Jennifer R Diamond
- Division of Medical Oncology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Christel Fontaine
- Medical Oncology Department, Oncologisch Centrum, UZ Brussel, Brussels, Belgium
| | | | - Hope S Rugo
- Department of Medicine, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA
| | - Sara A Hurvitz
- Department of Medicine, Division of Hematology/Oncology, David Geffen School of Medicine, University of California, Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA
| | - Kevin Kalinsky
- Winship Cancer Institute, Emory University, Atlanta, GA, USA
| | - Joyce O'Shaughnessy
- Baylor University Medical Center, Texas Oncology, US Oncology, Dallas, TX, USA
| | - Sibylle Loibl
- Department of Medicine and Research, Hämatologisch-Onkologische Gemeinschaftspraxis am Bethanien-Krankenhaus, Frankfurt, Germany
| | - Luca Gianni
- Medical Oncology, Gianni Bonadonna Foundation, Milan, Italy
| | - Martine Piccart
- Medical Oncology Department, Institut Jules Bordet and l'Université Libre de Bruxelles, Brussels, Belgium
| | - Yanni Zhu
- Department of Biostatistics, Gilead Sciences, Inc, Foster City, CA, USA
| | - Rosemary Delaney
- Department of Clinical Research, Gilead Sciences, Inc, Morris Plains, NJ, USA
| | - See Phan
- Department of Clinical Development, Gilead Sciences Inc, Foster City, CA, USA
| | - Javier Cortés
- International Breast Cancer Center, Quirón Group, Barcelona, Universidad Europea de Madrid, Faculty of Biomedical and Health Sciences, Department of Medicine, Madrid, Vall d´Hebron Institute of Oncology (VHIO), Barcelona, Spain
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19
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Miglietta F, Bottosso M, Griguolo G, Dieci MV, Guarneri V. Major advancements in metastatic breast cancer treatment: when expanding options means prolonging survival. ESMO Open 2022; 7:100409. [PMID: 35227965 PMCID: PMC8886005 DOI: 10.1016/j.esmoop.2022.100409] [Citation(s) in RCA: 43] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Revised: 01/12/2022] [Accepted: 01/22/2022] [Indexed: 12/13/2022] Open
Abstract
In the last years we have witnessed tremendous advancements in the treatment landscape of metastatic breast cancer (MBC), leading to a progressive prolongation of progression-free survival and, in some cases, also of overall survival. This led to a substantial increase of advanced disease treatability. In the present review we comprehensively and critically describe the most significant progresses in the therapeutic scenario of MBC according to BC subtype. In particular, we reviewed studies reporting practice-changing data in hormone receptor-positive/human epidermal growth factor receptor 2 (HER2)-negative, HER2-positive and triple-negative BC, with also a hint to BRCA-related tumors and the emerging HER2-low-positive category.
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Affiliation(s)
- F Miglietta
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
| | - M Bottosso
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
| | - G Griguolo
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy; Division of Oncology 2, Istituto Oncologico Veneto IRCCS, Padova, Italy
| | - M V Dieci
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy; Division of Oncology 2, Istituto Oncologico Veneto IRCCS, Padova, Italy
| | - V Guarneri
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy; Division of Oncology 2, Istituto Oncologico Veneto IRCCS, Padova, Italy.
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20
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Twelves C, Bartsch R, Ben-Baruch NE, Borstnar S, Dirix L, Tesarova P, Timcheva C, Zhukova L, Pivot X. The Place of Chemotherapy in The Evolving Treatment Landscape for Patients With HR-positive/HER2-negative MBC. Clin Breast Cancer 2022; 22:223-234. [PMID: 34844889 DOI: 10.1016/j.clbc.2021.10.007] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2021] [Revised: 07/23/2021] [Accepted: 10/19/2021] [Indexed: 11/19/2022]
Abstract
Endocrine therapy (ET) for the treatment of patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR-positive/HER2-negative) metastatic breast cancer (MBC) has changed markedly over recent years with the emergence of new ETs and the use of molecularly targeted agents. Cytotoxic chemotherapy continues, however, to have an important role in these patients and it is important to maximize its efficacy while minimizing toxicity to optimize outcomes. This review examines current HR-positive/HER2-negative MBC clinical guidelines and addresses key questions around the use of chemotherapy in the face of emerging therapeutic options. Specifically, the indications for chemotherapy in patients with HR-positive/HER2-negative MBC and the choice of optimal chemotherapy are discussed.
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Affiliation(s)
- Chris Twelves
- Clinical Cancer Pharmacology and Oncology, Leeds Institute of Medical Research, University of Leeds and Leeds Teaching Hospitals Trust Leeds.
| | - Rupert Bartsch
- Department of Medicine 1, Division of Oncology, Medical University of Vienna, Austria
| | | | - Simona Borstnar
- Division of Medical Oncology, Institute of Oncology, Ljubljana, Slovenia
| | - Luc Dirix
- Medical Oncology, Sint-Augustinus Hospital, Antwerp, Belgium
| | - Petra Tesarova
- First Faculty of Medicine and General Teaching Hospital, Charles University, Prague, Czech Republic
| | | | | | - Xavier Pivot
- ICANS - Strasbourg Europe Cancerology Institute, Strasbourg, France
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21
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Hall PE, Schmid P. Emerging strategies for TNBC with early clinical data: new chemoimmunotherapy strategies. Breast Cancer Res Treat 2022; 193:21-35. [PMID: 35235095 DOI: 10.1007/s10549-022-06547-x] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2021] [Accepted: 02/20/2022] [Indexed: 12/19/2022]
Abstract
PURPOSE The use of immune checkpoint inhibitors in combination with chemotherapy for the treatment of triple-negative breast cancer is becoming more widespread as efficacy data accumulates. However, outcomes remain less than optimal and not all patients benefit from treatment. The aim of this article is to review the emerging chemoimmunotherapy strategies for triple-negative breast cancer. METHODS Searches were undertaken on Pubmed and Clinicaltrials.gov for relevant publications and trials. RESULTS Preclinical and clinical data have provided insights into the differing immunomodulatory effects of chemotherapy agents, highlighting the immunostimulatory properties of anthracyclines. Mechanisms of resistance to immune checkpoint inhibition are discussed and the potential role of phosphatidylinositol 3-kinase (PI3K)/AKT and MAPK/ERK kinase (MEK) inhibitors in overcoming resistance. Finally, the emerging therapeutic class of antibody-drug conjugates for triple-negative breast cancer in combination with immune checkpoint inhibitors is reviewed. CONCLUSIONS The type and sequence of chemotherapy agents play an important role in optimising the response to immune checkpoint inhibitors. Antibody-drug conjugates in combination with immune checkpoint inhibitors are a promising area of development.
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Affiliation(s)
- Peter E Hall
- Department of Medical Oncology, St Bartholomew's Hospital, King George V Building, West Smithfield, London, EC1A 7BE, UK.
| | - Peter Schmid
- Department of Medical Oncology, St Bartholomew's Hospital, King George V Building, West Smithfield, London, EC1A 7BE, UK.,Barts Cancer Institute, Queen Mary University of London, London, UK
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22
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Nakamoto S, Watanabe J, Ohtani S, Morita S, Ikeda M. Eribulin improved the overall survival from the initiation of first-line chemotherapy for HER2-negative advanced breast cancer: a multicenter retrospective study. BMC Cancer 2022; 22:31. [PMID: 34980019 PMCID: PMC8722338 DOI: 10.1186/s12885-021-09137-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2021] [Accepted: 12/22/2021] [Indexed: 11/10/2022] Open
Abstract
Background Eribulin methylate (eribulin) improved the overall survival (OS) of eribulin-treated patients with HER2-negative advanced breast cancer (ABC) in prospective and retrospective studies. However, the effect of eribulin on OS as first-line chemotherapy and the characteristics of the patients who benefited from eribulin remain unclear. Methods Between January 2011 and December 2016, 301 patients with HER2-negative ABC who started first-line chemotherapy at 3 institutions were retrospectively evaluated for OS from the initiation of first-line chemotherapy. Results We identified 172 patients (119 estrogen receptor-positive [ER+], 47 ER−, 6 unknown) who received eribulin (eribulin group) and 129 patients (92 ER+, 31 ER−, 6 unknown) who did not receive eribulin (non-eribulin group). The median OS from the initiation of first-line chemotherapy in the two groups was not statistically significant (869 vs. 744 days, P = 0.47, log-rank); however, in patients who received eribulin in later lines (≥3rd-line) and who had a history of perioperative chemotherapy with anthracycline- and/or taxane-based regimens, the median OS improved (1001 vs. 744 days, P = 0.037; and 834 vs. 464 days, respectively P = 0.032, respectively; Wilcoxon). Multivariate analyses revealed that a history of perioperative chemotherapy with anthracycline- and/or taxane-based regimens was a predictive factor (hazard ratio, 0.39; 95% confidence interval, 0.21–0.70) for OS. Conclusions This study successfully identified subgroups of HER2− ABC patients with improved OS by eribulin therapy. Selecting patients according to their background and line of treatment will maximize the efficacy of eribulin therapy.
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Affiliation(s)
- Shogo Nakamoto
- Division of Breast Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi, Shizuoka, 411-8777, Japan. .,Division of Breast and Thyroid Gland Surgery, Fukuyama City Hospital, 5-23-1 Zao, Fukuyama, Hiroshima, 721-8511, Japan.
| | - Junichiro Watanabe
- Division of Breast Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi, Shizuoka, 411-8777, Japan
| | - Shoichiro Ohtani
- Division of Breast Surgery, Hiroshima City Hiroshima Citizens Hospital, 7-33 Motomachi, Naka-ku, Hiroshima, Hiroshima, 730-8518, Japan
| | - Satoshi Morita
- Division of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Yoshida-Konoe, Sakyo-ku, Kyoto, 606-8501, Japan
| | - Masahiko Ikeda
- Division of Breast and Thyroid Gland Surgery, Fukuyama City Hospital, 5-23-1 Zao, Fukuyama, Hiroshima, 721-8511, Japan
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23
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Umemneku-Chikere CM, Ayodele O, Soares M, Khan S, Abrams K, Owen R, Bujkiewicz S. Comparative review of pharmacological therapies in individuals with HER2-positive advanced breast cancer with focus on hormone receptor subgroups. Front Oncol 2022; 12:943154. [PMID: 36059633 PMCID: PMC9433866 DOI: 10.3389/fonc.2022.943154] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Accepted: 07/22/2022] [Indexed: 11/13/2022] Open
Abstract
Breast cancer is the fifth leading cause of cancer-related deaths worldwide. The randomized controlled trials (RCTs) of targeted therapies in human epidermal receptor 2 (HER2)-positive advanced breast cancer (ABC) have provided an evidence base for regulatory and reimbursement agencies to appraise the use of cancer therapies in clinical practice. However, a subset of these patients harbor additional biomarkers, for example, a positive hormone receptor status that may be more amenable to therapy and improve overall survival (OS). This review seeks to explore the reporting of evidence for treatment effects by the hormone receptor status using the RCT evidence of targeted therapies for HER2-positive ABC patients. Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were followed to identify published RCTs. Extracted data were synthesized using network meta-analysis to obtain the relative effects of HER2-positive-targeted therapies. We identified a gap in the reporting of the effectiveness of therapies by the hormone receptor status as only 15 out of 42 identified RCTs reported hormone receptor subgroup analyses; the majority of which reported progression-free survival but not OS or the overall response rate. In conclusion, we recommend that future trials in ABC should report the effect of cancer therapies in hormone receptor subgroups for all outcomes.
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Affiliation(s)
| | - Olubukola Ayodele
- University Hospital Leicester National Health Service (NHS) Trust, Leicester Royal Infirmary, Leicester, United Kingdom
| | - Marta Soares
- Centre for Health Economics, University of York, York, United Kingdom
| | - Sam Khan
- Leicester Cancer Research Centre, University of Leicester, Leicester, United Kingdom
| | - Keith Abrams
- Department of Statistics, University of Warwick, Coventry, United Kingdom
| | - Rhiannon Owen
- Medical School, Swansea University, Swansea, United Kingdom
| | - Sylwia Bujkiewicz
- Biostatistics Research Group, Department of Health Sciences, University of Leicester, Leicester, United Kingdom
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24
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Prioritising systemic cancer therapies applying ESMO’s tools and other resources to assist in improving cancer care globally: the Kazakh experience. ESMO Open 2022; 7:100362. [PMID: 35246325 PMCID: PMC8897160 DOI: 10.1016/j.esmoop.2021.100362] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2021] [Revised: 11/27/2021] [Accepted: 11/30/2021] [Indexed: 11/20/2022] Open
Abstract
Background In Kazakhstan, cancer is the second leading cause of death with a major public health and economic burden. In the last decade, cancer care and cancer medicine costs have significantly increased. To improve the efficiency and efficacy of cancer care expenditure and planning, the Kazakhstan Ministry of Health requested assistance from the World Health Organization (WHO) and the European Society for Medical Oncology (ESMO) to review its systemic cancer treatment protocols and essential medicines list and identify high-impact, effective regimens. Materials and methods ESMO developed a four-phase approach to review Kazakhstan cancer treatment protocols: (i) perform a systematic analysis of the country’s cancer medicines and treatment protocols; (ii) cross-reference the country’s cancer protocols with the WHO Model List of Essential Medicines, the ESMO-Magnitude of Clinical Benefit Scale and the European Medicines Agency’s medicine availability and indications database; (iii) extract treatment recommendations from the ESMO Clinical Practice Guidelines; (iv) expert review for all cancer medicines not on the WHO Model List of Essential Medicines and the country treatment protocols. Results This ESMO four-phase approach led to the update of the Kazakhstan national essential cancer medicines list and the list of cancer treatment protocols. This review has led to the withdrawal of several low-value or non-evidence-based medicines and a budget increase for cancer care to include all essential and highly effective medicines and treatment options. Conclusion When applied effectively, this four-phase approach can improve access to medicines, efficiency of expenditure and sustainability of cancer systems. The WHO–ESMO collaboration illustrated how, by sharing best practices, tools and resources, we can address access to cancer medicines and positively impact patient care.
In Kazakhstan, from 2009 to 2019, there was a significant increase in costs of cancer care and cancer medicines. ESMO, under the guidance of WHO, reviewed the Kazakh cancer treatment protocols and national essential medicines list. The ESMO four-phase approach helped Kazakhstan in prioritising the most effective and high-impact cancer medicines. This approach can be applied in the evaluation of any national formulary as it uses open-access, evidence-based references. This collaboration is an example of how we can improve access to cancer medicines and positively impact patient care.
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25
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O'Shaughnessy J, Brufsky A, Rugo HS, Tolaney SM, Punie K, Sardesai S, Hamilton E, Loirat D, Traina T, Leon-Ferre R, Hurvitz SA, Kalinsky K, Bardia A, Henry S, Mayer I, Zhu Y, Phan S, Cortés J. Analysis of patients without and with an initial triple-negative breast cancer diagnosis in the phase 3 randomized ASCENT study of sacituzumab govitecan in metastatic triple-negative breast cancer. Breast Cancer Res Treat 2022; 195:127-139. [PMID: 35545724 PMCID: PMC9374646 DOI: 10.1007/s10549-022-06602-7] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Accepted: 04/06/2022] [Indexed: 12/14/2022]
Abstract
PURPOSE Sacituzumab govitecan (SG) is an antibody-drug conjugate composed of an anti-Trop-2 antibody coupled to SN-38 via a proprietary hydrolyzable linker. In the ASCENT study, SG improved survival versus single-agent treatment of physician's choice (TPC) in pre-treated metastatic triple-negative breast cancer (mTNBC). Hormone/HER2 receptor changes are common, particularly at relapse/metastasis. This subanalysis assessed outcomes in patients who did/did not have TNBC at initial diagnosis, before enrollment. METHODS TNBC diagnosis was only required at study entry. Patients with mTNBC refractory/relapsing after ≥ 2 prior chemotherapies were randomized 1:1 to receive SG or TPC. Primary endpoint was progression-free survival (PFS) in patients without brain metastases. RESULTS Overall, 70/235 (30%) and 76/233 (33%) patients who received SG and TPC, respectively, did not have TNBC at initial diagnosis. Clinical benefit with SG versus TPC was observed in this subset. Median PFS was 4.6 versus 2.3 months (HR 0.48; 95% CI 0.32-0.72), median overall survival was 12.4 versus 6.7 months (HR 0.44; 95% CI 0.30-0.64), and objective response rate (ORR) was 31% versus 4%; those who also received prior CDK4/6 inhibitors had ORRs of 21% versus 5%. Efficacy and safety for patients with TNBC at initial diagnosis were generally similar to those who did not present with TNBC at initial diagnosis. CONCLUSION Patients without TNBC at initial diagnosis had improved clinical outcomes and a manageable safety profile with SG, supporting SG as a treatment option for mTNBC regardless of subtype at initial diagnosis. Subtype reassessment in advanced breast cancer allows for optimal treatment. Clinical trial registration number NCT02574455, registered October 12, 2015.
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Affiliation(s)
- Joyce O'Shaughnessy
- Medical Oncology, Texas Oncology-Baylor Charles A. Sammons Cancer Center, 3410 Worth St., Suite 400, Dallas, TX, 75246, USA.
| | - Adam Brufsky
- Magee-Womens Hospital and the Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Hope S Rugo
- Department of Medicine, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA
| | - Sara M Tolaney
- Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Kevin Punie
- Department of General Medical Oncology and Multidisciplinary Breast Centre, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium
| | - Sagar Sardesai
- The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA
| | - Erika Hamilton
- Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN, USA
| | - Delphine Loirat
- Medical Oncology Department and D3i, Institut Curie, Paris, France
| | - Tiffany Traina
- Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | | | - Sara A Hurvitz
- Medical Oncology, University of California, Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA
| | - Kevin Kalinsky
- Columbia University Irving Medical Center, New York, NY, USA
- Winship Cancer Institute, Emory University, Atlanta, GA, USA
| | - Aditya Bardia
- Department of Hematology/Oncology, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, USA
| | - Stephanie Henry
- Department of Oncology-Hematology, Radiotherapy, and Nuclear Medicine, CHU UCL Namur, Namur, Belgium
| | - Ingrid Mayer
- Breast Cancer Program, Division of Hematology/Oncology, Vanderbilt-Ingram Cancer Center, Nashville, TN, USA
| | - Yanni Zhu
- Department of Biostatistics, Gilead Sciences, Inc., Foster City, CA, USA
| | - See Phan
- Department of Clinical Development, Gilead Sciences, Inc., Foster City, CA, USA
| | - Javier Cortés
- International Breast Cancer Center, Quironsalud Group, Barcelona, Spain
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Shorter duration of first-line chemotherapy reflects poorer outcomes in patients with HER2-negative advanced breast cancer: a multicenter retrospective study. Sci Rep 2021; 11:21454. [PMID: 34728668 PMCID: PMC8563944 DOI: 10.1038/s41598-021-00711-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2021] [Accepted: 10/15/2021] [Indexed: 11/09/2022] Open
Abstract
Post-progression survival affects overall survival (OS) in patients with HER2-negative advanced breast cancer (HER2-ABC); thus, the optimal choice of first-line chemotherapy (1LCT) remains controversial. We investigated patients with HER2-ABC focusing on their sensitivity to 1LCT. We retrospectively analyzed patients with HER2-ABC who received 1LCT between January 2011 and December 2016 in three participating institutions. We identified 149 patients in the shorter and 152 patients in the longer time to treatment failure (TTF) groups. The median OS was significantly longer in the longer TTF group (hazard ratio [HR] 0.44, P < 0.001, log-rank). In the shorter TTF group, OS of patients who received paclitaxel plus bevacizumab (PB) therapy was significantly inferior to that of those who received chemotherapy other than PB (HR 2.57, P < 0.001, log-rank), and subsequent eribulin therapy significantly improved OS from 1LCT initiation (Wilcoxon P < 0.001); multivariate analyses showed that 1LCT PB therapy was an independent risk factor for poorer OS (HR 2.05, P = 0.003), while subsequent eribulin therapy was an independent prognostic factor for better OS (HR 0.56, P = 0.004). OS was significantly poorer in patients with HER2-ABC with a shorter duration of 1LCT, including PB therapy, while subsequent eribulin therapy improved OS.
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27
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Díaz-Acedo R, Artacho Criado S, Jiménez Galán R, Gutiérrez Pizarraya A, Galván Banqueri M, Rodríguez-de-la-Borbolla-Artacho M, Marcos Rodríguez JA, Márquez Saavedra E. Effectiveness and safety of eribulin for human epidermal growth factor receptor 2 negative metastatic breast cancer in a real-world population. J Oncol Pharm Pract 2021; 28:1573-1582. [PMID: 34558360 DOI: 10.1177/10781552211038241] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
BACKGROUND Eribulin's clinical benefit remains unclear; so, studies analyzing its effectiveness in routine clinical practice are interesting. PATIENTS AND METHODS This is a multicenter, retrospective study including patients with human epidermal growth factor receptor-2-negative metastatic breast cancer which assesses effectiveness and safety of eribulin. RESULTS A total of 140 women were included, with a median age of 57 years. The median overall survival and progression-free survival were 8.8 (95% confidence interval: 6.1-11.4) and 2.8 months (95% confidence interval: 2.5-3.1), respectively. For patients with hormonal receptor expression, a significantly longer progression-free survival was observed: 3.4 (95%confidence interval: 2.3-4.5) versus triple negative: 2.0 (95%confidence interval: 1.7-2.3) months, p = 0.003. Also, those who had received capecitabine prior to eribulin had a higher median overall survival than those who had not received it (9.5 months, 95% confidence interval: 6.6-12.5 vs. 4.8 months, 95% confidence interval: 3.4-6.2; p = 0.001). When only triple-negative patients were included, median overall survival was 6.5 (95% confidence interval: 0.1-16.2) for those who had received previous capecitabine versus 4.3 (95% confidence interval: 2.8-5.8) months for patients who had not received it; p =0.006. The safety profile of eribulin was adequate. CONCLUSION Effectiveness of eribulin in a real-life human epidermal growth factor receptor-2--negative population is lower than that observed in clinical trials. Its benefit seems to be higher in patients with hormonal receptor expression and patients who had received capecitabine prior to eribulin. The safety profile of eribulin is adequate.
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28
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Hoon SN, Lau PK, White AM, Bulsara MK, Banks PD, Redfern AD. Capecitabine for hormone receptor-positive versus hormone receptor-negative breast cancer. Cochrane Database Syst Rev 2021; 5:CD011220. [PMID: 34037241 PMCID: PMC8150746 DOI: 10.1002/14651858.cd011220.pub2] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
BACKGROUND Retrospective analyses suggest that capecitabine may carry superior activity in hormone receptor-positive relative to hormone receptor-negative metastatic breast cancer. This review examined the veracity of that finding and explored whether this differential activity extends to early breast cancer. OBJECTIVES To assess effects of chemotherapy regimens containing capecitabine compared with regimens not containing capecitabine for women with hormone receptor-positive versus hormone receptor-negative breast cancer across the three major treatment scenarios: neoadjuvant, adjuvant, metastatic. SEARCH METHODS On 4 June 2019, we searched the Cochrane Breast Cancer Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 5) in the Cochrane Library; MEDLINE; Embase; the World Health Organization International Clinical Trials Registry Platform; and ClinicalTrials.gov. SELECTION CRITERIA Randomised controlled trials looking at chemotherapy regimens containing capecitabine alone or in combination with other agents versus a control or similar regimen without capecitabine for treatment of breast cancer at any stage. The primary outcome measure for metastatic and adjuvant trials was overall survival (OS), and for neoadjuvant studies pathological complete response (pCR). DATA COLLECTION AND ANALYSIS Two review authors independently extracted data and assessed risk of bias and certainty of evidence using the GRADE approach. Hazard ratios (HRs) were derived for time-to-event outcomes, and odds ratios (ORs) for dichotomous outcomes, and meta-analysis was performed using a fixed-effect model. MAIN RESULTS We included 26 studies with outcome data by hormone receptor: 12 metastatic studies (n = 4325), 6 neoadjuvant trials (n = 3152), and 8 adjuvant studies (n = 13,457). Capecitabine treatment was added in several different ways across studies. These could be classified as capecitabine alone compared to another treatment, capecitabine substituted for part of the control chemotherapy, and capecitabine added to control chemotherapy. In the metastatic setting, the effect of capecitabine was heterogenous between hormone receptor-positive and -negative tumours. For OS, no difference between capecitabine-containing and non-capecitabine-containing regimens was observed for all participants taken together (HR 1.01, 95% confidence interval (CI) 0.98 to 1.05; 12 studies, 4325 participants; high-certainty evidence), for those with hormone receptor-positive disease (HR 0.93, 95% CI 0.84 to 1.04; 7 studies, 1834 participants; high-certainty evidence), and for those with hormone receptor-negative disease (HR 1.00, 95% CI 0.88 to 1.13; 8 studies, 1577 participants; high-certainty evidence). For progression-free survival (PFS), a small improvement was seen for all people (HR 0.89, 95% CI 0.82 to 0.96; 12 studies, 4325 participants; moderate-certainty evidence). This was largely accounted for by a moderate improvement in PFS for inclusion of capecitabine in hormone receptor-positive cancers (HR 0.82, 95% CI 0.73 to 0.91; 7 studies, 1594 participants; moderate-certainty evidence) compared to no difference in PFS for hormone receptor-negative cancers (HR 0.96, 95% CI 0.83 to 1.10; 7 studies, 1122 participants; moderate-certainty evidence). Quality of life was assessed in five studies; in general there did not seem to be differences in global health scores between the two treatment groups at around two years' follow-up. Neoadjuvant studies were highly variable in design, having been undertaken to test various experimental regimens using pathological complete response (pCR) as a surrogate for disease-free survival (DFS) and OS. Across all patients, capecitabine-containing regimens resulted in little difference in pCR in comparison to non-capecitabine-containing regimens (odds ratio (OR) 1.12, 95% CI 0.94 to 1.33; 6 studies, 3152 participants; high-certainty evidence). By subtype, no difference in pCR was observed for either hormone receptor-positive (OR 1.22, 95% CI 0.76 to 1.95; 4 studies, 964 participants; moderate-certainty evidence) or hormone receptor-negative tumours (OR 1.28, 95% CI 0.61 to 2.66; 4 studies, 646 participants; moderate-certainty evidence). Four studies with 2460 people reported longer-term outcomes: these investigators detected no difference in either DFS (HR 1.02, 95% CI 0.86 to 1.21; high-certainty evidence) or OS (HR 0.97, 95% CI 0.77 to 1.23; high-certainty evidence). In the adjuvant setting, a modest improvement in OS was observed across all participants (HR 0.89, 95% CI 0.81 to 0.98; 8 studies, 13,547 participants; moderate-certainty evidence), and no difference in OS was seen in hormone receptor-positive cancers (HR 0.86, 95% CI 0.68 to 1.09; 3 studies, 3683 participants), whereas OS improved in hormone receptor-negative cancers (HR 0.72, 95% CI 0.59 to 0.89; 5 studies, 3432 participants). No difference in DFS or relapse-free survival (RFS) was observed across all participants (HR 0.93, 95% CI 0.86 to 1.01; 8 studies, 13,457 participants; moderate-certainty evidence). As was observed for OS, no difference in DFS/RFS was seen in hormone receptor-positive cancers (HR 1.03, 95% CI 0.91 to 1.17; 5 studies, 5604 participants; moderate-certainty evidence), and improvements in DFS/RFS with inclusion of capecitabine were observed for hormone receptor-negative cancers (HR 0.74, 95% CI 0.64 to 0.86; 7 studies, 3307 participants; moderate-certainty evidence). Adverse effects were reported across all three scenarios. When grade 3 or 4 febrile neutropenia was considered, no difference was seen for capecitabine compared to non-capecitabine regimens in neoadjuvant studies (OR 1.31, 95% CI 0.97 to 1.77; 4 studies, 2890 participants; moderate-certainty evidence), and a marked reduction was seen for capecitabine in adjuvant studies (OR 0.55, 95% CI 0.47 to 0.64; 5 studies, 8086 participants; moderate-certainty evidence). There was an increase in diarrhoea and hand-foot syndrome in neoadjuvant (diarrhoea: OR 1.95, 95% CI 1.32 to 2.89; 3 studies, 2686 participants; hand-foot syndrome: OR 6.77, 95% CI 4.89 to 9.38; 5 studies, 3021 participants; both moderate-certainty evidence) and adjuvant trials (diarrhoea: OR 2.46, 95% CI 2.01 to 3.01; hand-foot syndrome: OR 13.60, 95% CI 10.65 to 17.37; 8 studies, 11,207 participants; moderate-certainty evidence for both outcomes). AUTHORS' CONCLUSIONS In summary, a moderate PFS benefit by including capecitabine was seen only in hormone receptor-positive cancers in metastatic studies. No benefit of capecitabine for pCR was noted overall or in hormone receptor subgroups when included in neoadjuvant therapy. In contrast, the addition of capecitabine in the adjuvant setting led to improved outcomes for OS and DFS in hormone receptor-negative cancer. Future studies should stratify by hormone receptor and triple-negative breast cancer (TNBC) status to clarify the differential effects of capecitabine in these subgroups across all treatment scenarios, to optimally guide capecitabine inclusion.
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Affiliation(s)
- Siao-Nge Hoon
- Medical Oncology Department, St John of God Midland, Perth, Australia
- Medical Oncology Department, Sir Charles Gairdner Hospital, Perth, Australia
| | - Peter Kh Lau
- Medical Oncology Department, Sir Charles Gairdner Hospital, Perth, Australia
- Medical Oncology Department, Peter MacCallum Cancer Centre, Melbourne, Australia
| | - Alison M White
- Murdoch Community Hospice, St John of God Hospital Murdoch, Perth, Australia
- Palliative Care Department, Royal Perth Hospital, Perth, Australia
| | - Max K Bulsara
- Institute for Health Research, University of Notre Dame Australia, Fremantle, Australia
- School of Population and Global Health, The University of Western Australia, Perth, Australia
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Patricia D Banks
- Medical Oncology Department, Peter MacCallum Cancer Centre, Melbourne, Australia
- Medical Oncology Department, University Hospital Geelong, Geelong, Australia
| | - Andrew D Redfern
- School of Medicine, University of Western Australia, Perth, Australia
- Medical Oncology Department, Fiona Stanley Hospital, Perth, Australia
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Furuuchi K, Rybinski K, Fulmer J, Moriyama T, Drozdowski B, Soto A, Fernando S, Wilson K, Milinichik A, Dula ML, Tanaka K, Cheng X, Albone E, Uenaka T. Antibody-drug conjugate MORAb-202 exhibits long-lasting antitumor efficacy in TNBC PDx models. Cancer Sci 2021; 112:2467-2480. [PMID: 33756060 PMCID: PMC8177789 DOI: 10.1111/cas.14898] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Revised: 03/16/2021] [Accepted: 03/19/2021] [Indexed: 12/17/2022] Open
Abstract
The antibody‐drug conjugate (ADC) MORAb‐202, consisting of farletuzumab paired with a cathepsin B–cleavable linker and eribulin, targets folate receptor alpha (FRA), which is frequently overexpressed in various tumor types. MORAb‐202 was highly cytotoxic to FRA‐positive cells in vitro, with limited off‐target killing of FRA‐negative cells. Furthermore, MORAb‐202 showed a clear in vitro bystander cytotoxic effect in coculture with FRA‐positive/negative cells. In vivo antitumor efficacy studies of MORAb‐202 were conducted with a single administration of MORAb‐202 in triple‐negative breast cancer (TNBC) patient–derived xenograft (PDx) models expressing low and high levels of FRA. MORAb‐202 exhibited durable efficacy proportional to tumor FRA expression. Toxicology studies (Q3Wx2) in nonhuman primates suggested that the major observed toxicity of MORAb‐202 is hematologic toxicity. Overall, these findings support the concept that MORAb‐202 represents a promising investigational ADC for the treatment of TNBC patients.
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Affiliation(s)
- Keiji Furuuchi
- Epochal Precision Anti-Cancer Therapeutics (EPAT), Eisai Inc, Exton, PA, USA
| | - Katherine Rybinski
- Epochal Precision Anti-Cancer Therapeutics (EPAT), Eisai Inc, Exton, PA, USA
| | - James Fulmer
- Epochal Precision Anti-Cancer Therapeutics (EPAT), Eisai Inc, Exton, PA, USA
| | | | - Brian Drozdowski
- Epochal Precision Anti-Cancer Therapeutics (EPAT), Eisai Inc, Exton, PA, USA
| | - Allis Soto
- Epochal Precision Anti-Cancer Therapeutics (EPAT), Eisai Inc, Exton, PA, USA
| | - Shawn Fernando
- Epochal Precision Anti-Cancer Therapeutics (EPAT), Eisai Inc, Exton, PA, USA
| | - Kerrianne Wilson
- Epochal Precision Anti-Cancer Therapeutics (EPAT), Eisai Inc, Exton, PA, USA
| | - Andrew Milinichik
- Epochal Precision Anti-Cancer Therapeutics (EPAT), Eisai Inc, Exton, PA, USA
| | - Mary Lou Dula
- Epochal Precision Anti-Cancer Therapeutics (EPAT), Eisai Inc, Exton, PA, USA
| | - Keigo Tanaka
- Tsukuba Research Laboratory, Eisai, Co. Ltd, Tsukuba, Japan
| | - Xin Cheng
- Epochal Precision Anti-Cancer Therapeutics (EPAT), Eisai Inc, Exton, PA, USA
| | - Earl Albone
- Epochal Precision Anti-Cancer Therapeutics (EPAT), Eisai Inc, Exton, PA, USA
| | - Toshimitsu Uenaka
- Epochal Precision Anti-Cancer Therapeutics (EPAT), Eisai Inc, Exton, PA, USA
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30
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Bardia A, Hurvitz SA, Tolaney SM, Loirat D, Punie K, Oliveira M, Brufsky A, Sardesai SD, Kalinsky K, Zelnak AB, Weaver R, Traina T, Dalenc F, Aftimos P, Lynce F, Diab S, Cortés J, O'Shaughnessy J, Diéras V, Ferrario C, Schmid P, Carey LA, Gianni L, Piccart MJ, Loibl S, Goldenberg DM, Hong Q, Olivo MS, Itri LM, Rugo HS. Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer. N Engl J Med 2021; 384:1529-1541. [PMID: 33882206 DOI: 10.1056/nejmoa2028485] [Citation(s) in RCA: 817] [Impact Index Per Article: 204.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
BACKGROUND Patients with metastatic triple-negative breast cancer have a poor prognosis. Sacituzumab govitecan is an antibody-drug conjugate composed of an antibody targeting the human trophoblast cell-surface antigen 2 (Trop-2), which is expressed in the majority of breast cancers, coupled to SN-38 (topoisomerase I inhibitor) through a proprietary hydrolyzable linker. METHODS In this randomized, phase 3 trial, we evaluated sacituzumab govitecan as compared with single-agent chemotherapy of the physician's choice (eribulin, vinorelbine, capecitabine, or gemcitabine) in patients with relapsed or refractory metastatic triple-negative breast cancer. The primary end point was progression-free survival (as determined by blinded independent central review) among patients without brain metastases. RESULTS A total of 468 patients without brain metastases were randomly assigned to receive sacituzumab govitecan (235 patients) or chemotherapy (233 patients). The median age was 54 years; all the patients had previous use of taxanes. The median progression-free survival was 5.6 months (95% confidence interval [CI], 4.3 to 6.3; 166 events) with sacituzumab govitecan and 1.7 months (95% CI, 1.5 to 2.6; 150 events) with chemotherapy (hazard ratio for disease progression or death, 0.41; 95% CI, 0.32 to 0.52; P<0.001). The median overall survival was 12.1 months (95% CI, 10.7 to 14.0) with sacituzumab govitecan and 6.7 months (95% CI, 5.8 to 7.7) with chemotherapy (hazard ratio for death, 0.48; 95% CI, 0.38 to 0.59; P<0.001). The percentage of patients with an objective response was 35% with sacituzumab govitecan and 5% with chemotherapy. The incidences of key treatment-related adverse events of grade 3 or higher were neutropenia (51% with sacituzumab govitecan and 33% with chemotherapy), leukopenia (10% and 5%), diarrhea (10% and <1%), anemia (8% and 5%), and febrile neutropenia (6% and 2%). There were three deaths owing to adverse events in each group; no deaths were considered to be related to sacituzumab govitecan treatment. CONCLUSIONS Progression-free and overall survival were significantly longer with sacituzumab govitecan than with single-agent chemotherapy among patients with metastatic triple-negative breast cancer. Myelosuppression and diarrhea were more frequent with sacituzumab govitecan. (Funded by Immunomedics; ASCENT ClinicalTrials.gov number, NCT02574455; EudraCT number, 2017-003019-21.).
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Affiliation(s)
- Aditya Bardia
- From the Division of Medical Oncology, Massachusetts General Hospital Cancer Center (A. Bardia), and the Department of Medical Oncology, Dana-Farber Cancer Institute (S.M.T.) - both in Boston; the University of California, Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles (S.A.H.); the Medical Oncology Department and the Department of Drug Development and Innovation, Institut Curie, Paris (D.L.), Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse Oncopole, Toulouse (F.D.), and the Department of Medical Oncology, Centre Eugène Marquis, Rennes (V.D.) - all in France; the Department of General Medical Oncology and Multidisciplinary Breast Center, Leuven Cancer Institute, University Hospitals Leuven, Leuven (K.P.), and the Clinical Trials Conduct Unit (P.A.), Institut Jules Bordet-Université Libre de Bruxelles (M.J.P.), Brussels - all in Belgium; the Medical Oncology Department and Breast Cancer Group, Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology (M.O.), and the International Breast Cancer Center, Quiron Group (J.C.) - all in Barcelona; Magee-Womens Hospital and the Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh (A. Brufsky); Ohio State University Wexner Medical Center, Columbus (S.D.S.); Columbia University Irving Medical Center (K.K.) and Memorial Sloan Kettering Cancer Center (T.T.) - both in New York; Northside Hospital, Atlanta (A.B.Z.); Florida Cancer Specialists, Tampa (R.W.); Georgetown Lombardi Comprehensive Cancer Center, Washington, DC (F.L.); Rocky Mountain Cancer Centers, Greenwood Village, CO (S.D.); Baylor University Medical Center and Texas Oncology, Dallas (J.O.); Segal Cancer Centre, Jewish General Hospital, Montreal (C.F.); Barts Cancer Institute, Queen Mary University of London, London (P.S.); University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill (L.A.C.); Gianni Bonadonna Foundation, Milan (L.G.); the Department of Medicine and Research, Hämatologisch-Onkologische Gemeinschaftspraxis am Bethanien-Krankenhaus, Frankfurt, Germany (S.L.); Immunomedics, Morris Plains, NJ (D.M.G., Q.H., M.S.O., L.M.I.); and the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco (H.S.R.)
| | - Sara A Hurvitz
- From the Division of Medical Oncology, Massachusetts General Hospital Cancer Center (A. Bardia), and the Department of Medical Oncology, Dana-Farber Cancer Institute (S.M.T.) - both in Boston; the University of California, Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles (S.A.H.); the Medical Oncology Department and the Department of Drug Development and Innovation, Institut Curie, Paris (D.L.), Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse Oncopole, Toulouse (F.D.), and the Department of Medical Oncology, Centre Eugène Marquis, Rennes (V.D.) - all in France; the Department of General Medical Oncology and Multidisciplinary Breast Center, Leuven Cancer Institute, University Hospitals Leuven, Leuven (K.P.), and the Clinical Trials Conduct Unit (P.A.), Institut Jules Bordet-Université Libre de Bruxelles (M.J.P.), Brussels - all in Belgium; the Medical Oncology Department and Breast Cancer Group, Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology (M.O.), and the International Breast Cancer Center, Quiron Group (J.C.) - all in Barcelona; Magee-Womens Hospital and the Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh (A. Brufsky); Ohio State University Wexner Medical Center, Columbus (S.D.S.); Columbia University Irving Medical Center (K.K.) and Memorial Sloan Kettering Cancer Center (T.T.) - both in New York; Northside Hospital, Atlanta (A.B.Z.); Florida Cancer Specialists, Tampa (R.W.); Georgetown Lombardi Comprehensive Cancer Center, Washington, DC (F.L.); Rocky Mountain Cancer Centers, Greenwood Village, CO (S.D.); Baylor University Medical Center and Texas Oncology, Dallas (J.O.); Segal Cancer Centre, Jewish General Hospital, Montreal (C.F.); Barts Cancer Institute, Queen Mary University of London, London (P.S.); University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill (L.A.C.); Gianni Bonadonna Foundation, Milan (L.G.); the Department of Medicine and Research, Hämatologisch-Onkologische Gemeinschaftspraxis am Bethanien-Krankenhaus, Frankfurt, Germany (S.L.); Immunomedics, Morris Plains, NJ (D.M.G., Q.H., M.S.O., L.M.I.); and the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco (H.S.R.)
| | - Sara M Tolaney
- From the Division of Medical Oncology, Massachusetts General Hospital Cancer Center (A. Bardia), and the Department of Medical Oncology, Dana-Farber Cancer Institute (S.M.T.) - both in Boston; the University of California, Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles (S.A.H.); the Medical Oncology Department and the Department of Drug Development and Innovation, Institut Curie, Paris (D.L.), Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse Oncopole, Toulouse (F.D.), and the Department of Medical Oncology, Centre Eugène Marquis, Rennes (V.D.) - all in France; the Department of General Medical Oncology and Multidisciplinary Breast Center, Leuven Cancer Institute, University Hospitals Leuven, Leuven (K.P.), and the Clinical Trials Conduct Unit (P.A.), Institut Jules Bordet-Université Libre de Bruxelles (M.J.P.), Brussels - all in Belgium; the Medical Oncology Department and Breast Cancer Group, Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology (M.O.), and the International Breast Cancer Center, Quiron Group (J.C.) - all in Barcelona; Magee-Womens Hospital and the Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh (A. Brufsky); Ohio State University Wexner Medical Center, Columbus (S.D.S.); Columbia University Irving Medical Center (K.K.) and Memorial Sloan Kettering Cancer Center (T.T.) - both in New York; Northside Hospital, Atlanta (A.B.Z.); Florida Cancer Specialists, Tampa (R.W.); Georgetown Lombardi Comprehensive Cancer Center, Washington, DC (F.L.); Rocky Mountain Cancer Centers, Greenwood Village, CO (S.D.); Baylor University Medical Center and Texas Oncology, Dallas (J.O.); Segal Cancer Centre, Jewish General Hospital, Montreal (C.F.); Barts Cancer Institute, Queen Mary University of London, London (P.S.); University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill (L.A.C.); Gianni Bonadonna Foundation, Milan (L.G.); the Department of Medicine and Research, Hämatologisch-Onkologische Gemeinschaftspraxis am Bethanien-Krankenhaus, Frankfurt, Germany (S.L.); Immunomedics, Morris Plains, NJ (D.M.G., Q.H., M.S.O., L.M.I.); and the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco (H.S.R.)
| | - Delphine Loirat
- From the Division of Medical Oncology, Massachusetts General Hospital Cancer Center (A. Bardia), and the Department of Medical Oncology, Dana-Farber Cancer Institute (S.M.T.) - both in Boston; the University of California, Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles (S.A.H.); the Medical Oncology Department and the Department of Drug Development and Innovation, Institut Curie, Paris (D.L.), Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse Oncopole, Toulouse (F.D.), and the Department of Medical Oncology, Centre Eugène Marquis, Rennes (V.D.) - all in France; the Department of General Medical Oncology and Multidisciplinary Breast Center, Leuven Cancer Institute, University Hospitals Leuven, Leuven (K.P.), and the Clinical Trials Conduct Unit (P.A.), Institut Jules Bordet-Université Libre de Bruxelles (M.J.P.), Brussels - all in Belgium; the Medical Oncology Department and Breast Cancer Group, Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology (M.O.), and the International Breast Cancer Center, Quiron Group (J.C.) - all in Barcelona; Magee-Womens Hospital and the Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh (A. Brufsky); Ohio State University Wexner Medical Center, Columbus (S.D.S.); Columbia University Irving Medical Center (K.K.) and Memorial Sloan Kettering Cancer Center (T.T.) - both in New York; Northside Hospital, Atlanta (A.B.Z.); Florida Cancer Specialists, Tampa (R.W.); Georgetown Lombardi Comprehensive Cancer Center, Washington, DC (F.L.); Rocky Mountain Cancer Centers, Greenwood Village, CO (S.D.); Baylor University Medical Center and Texas Oncology, Dallas (J.O.); Segal Cancer Centre, Jewish General Hospital, Montreal (C.F.); Barts Cancer Institute, Queen Mary University of London, London (P.S.); University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill (L.A.C.); Gianni Bonadonna Foundation, Milan (L.G.); the Department of Medicine and Research, Hämatologisch-Onkologische Gemeinschaftspraxis am Bethanien-Krankenhaus, Frankfurt, Germany (S.L.); Immunomedics, Morris Plains, NJ (D.M.G., Q.H., M.S.O., L.M.I.); and the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco (H.S.R.)
| | - Kevin Punie
- From the Division of Medical Oncology, Massachusetts General Hospital Cancer Center (A. Bardia), and the Department of Medical Oncology, Dana-Farber Cancer Institute (S.M.T.) - both in Boston; the University of California, Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles (S.A.H.); the Medical Oncology Department and the Department of Drug Development and Innovation, Institut Curie, Paris (D.L.), Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse Oncopole, Toulouse (F.D.), and the Department of Medical Oncology, Centre Eugène Marquis, Rennes (V.D.) - all in France; the Department of General Medical Oncology and Multidisciplinary Breast Center, Leuven Cancer Institute, University Hospitals Leuven, Leuven (K.P.), and the Clinical Trials Conduct Unit (P.A.), Institut Jules Bordet-Université Libre de Bruxelles (M.J.P.), Brussels - all in Belgium; the Medical Oncology Department and Breast Cancer Group, Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology (M.O.), and the International Breast Cancer Center, Quiron Group (J.C.) - all in Barcelona; Magee-Womens Hospital and the Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh (A. Brufsky); Ohio State University Wexner Medical Center, Columbus (S.D.S.); Columbia University Irving Medical Center (K.K.) and Memorial Sloan Kettering Cancer Center (T.T.) - both in New York; Northside Hospital, Atlanta (A.B.Z.); Florida Cancer Specialists, Tampa (R.W.); Georgetown Lombardi Comprehensive Cancer Center, Washington, DC (F.L.); Rocky Mountain Cancer Centers, Greenwood Village, CO (S.D.); Baylor University Medical Center and Texas Oncology, Dallas (J.O.); Segal Cancer Centre, Jewish General Hospital, Montreal (C.F.); Barts Cancer Institute, Queen Mary University of London, London (P.S.); University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill (L.A.C.); Gianni Bonadonna Foundation, Milan (L.G.); the Department of Medicine and Research, Hämatologisch-Onkologische Gemeinschaftspraxis am Bethanien-Krankenhaus, Frankfurt, Germany (S.L.); Immunomedics, Morris Plains, NJ (D.M.G., Q.H., M.S.O., L.M.I.); and the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco (H.S.R.)
| | - Mafalda Oliveira
- From the Division of Medical Oncology, Massachusetts General Hospital Cancer Center (A. Bardia), and the Department of Medical Oncology, Dana-Farber Cancer Institute (S.M.T.) - both in Boston; the University of California, Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles (S.A.H.); the Medical Oncology Department and the Department of Drug Development and Innovation, Institut Curie, Paris (D.L.), Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse Oncopole, Toulouse (F.D.), and the Department of Medical Oncology, Centre Eugène Marquis, Rennes (V.D.) - all in France; the Department of General Medical Oncology and Multidisciplinary Breast Center, Leuven Cancer Institute, University Hospitals Leuven, Leuven (K.P.), and the Clinical Trials Conduct Unit (P.A.), Institut Jules Bordet-Université Libre de Bruxelles (M.J.P.), Brussels - all in Belgium; the Medical Oncology Department and Breast Cancer Group, Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology (M.O.), and the International Breast Cancer Center, Quiron Group (J.C.) - all in Barcelona; Magee-Womens Hospital and the Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh (A. Brufsky); Ohio State University Wexner Medical Center, Columbus (S.D.S.); Columbia University Irving Medical Center (K.K.) and Memorial Sloan Kettering Cancer Center (T.T.) - both in New York; Northside Hospital, Atlanta (A.B.Z.); Florida Cancer Specialists, Tampa (R.W.); Georgetown Lombardi Comprehensive Cancer Center, Washington, DC (F.L.); Rocky Mountain Cancer Centers, Greenwood Village, CO (S.D.); Baylor University Medical Center and Texas Oncology, Dallas (J.O.); Segal Cancer Centre, Jewish General Hospital, Montreal (C.F.); Barts Cancer Institute, Queen Mary University of London, London (P.S.); University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill (L.A.C.); Gianni Bonadonna Foundation, Milan (L.G.); the Department of Medicine and Research, Hämatologisch-Onkologische Gemeinschaftspraxis am Bethanien-Krankenhaus, Frankfurt, Germany (S.L.); Immunomedics, Morris Plains, NJ (D.M.G., Q.H., M.S.O., L.M.I.); and the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco (H.S.R.)
| | - Adam Brufsky
- From the Division of Medical Oncology, Massachusetts General Hospital Cancer Center (A. Bardia), and the Department of Medical Oncology, Dana-Farber Cancer Institute (S.M.T.) - both in Boston; the University of California, Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles (S.A.H.); the Medical Oncology Department and the Department of Drug Development and Innovation, Institut Curie, Paris (D.L.), Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse Oncopole, Toulouse (F.D.), and the Department of Medical Oncology, Centre Eugène Marquis, Rennes (V.D.) - all in France; the Department of General Medical Oncology and Multidisciplinary Breast Center, Leuven Cancer Institute, University Hospitals Leuven, Leuven (K.P.), and the Clinical Trials Conduct Unit (P.A.), Institut Jules Bordet-Université Libre de Bruxelles (M.J.P.), Brussels - all in Belgium; the Medical Oncology Department and Breast Cancer Group, Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology (M.O.), and the International Breast Cancer Center, Quiron Group (J.C.) - all in Barcelona; Magee-Womens Hospital and the Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh (A. Brufsky); Ohio State University Wexner Medical Center, Columbus (S.D.S.); Columbia University Irving Medical Center (K.K.) and Memorial Sloan Kettering Cancer Center (T.T.) - both in New York; Northside Hospital, Atlanta (A.B.Z.); Florida Cancer Specialists, Tampa (R.W.); Georgetown Lombardi Comprehensive Cancer Center, Washington, DC (F.L.); Rocky Mountain Cancer Centers, Greenwood Village, CO (S.D.); Baylor University Medical Center and Texas Oncology, Dallas (J.O.); Segal Cancer Centre, Jewish General Hospital, Montreal (C.F.); Barts Cancer Institute, Queen Mary University of London, London (P.S.); University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill (L.A.C.); Gianni Bonadonna Foundation, Milan (L.G.); the Department of Medicine and Research, Hämatologisch-Onkologische Gemeinschaftspraxis am Bethanien-Krankenhaus, Frankfurt, Germany (S.L.); Immunomedics, Morris Plains, NJ (D.M.G., Q.H., M.S.O., L.M.I.); and the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco (H.S.R.)
| | - Sagar D Sardesai
- From the Division of Medical Oncology, Massachusetts General Hospital Cancer Center (A. Bardia), and the Department of Medical Oncology, Dana-Farber Cancer Institute (S.M.T.) - both in Boston; the University of California, Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles (S.A.H.); the Medical Oncology Department and the Department of Drug Development and Innovation, Institut Curie, Paris (D.L.), Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse Oncopole, Toulouse (F.D.), and the Department of Medical Oncology, Centre Eugène Marquis, Rennes (V.D.) - all in France; the Department of General Medical Oncology and Multidisciplinary Breast Center, Leuven Cancer Institute, University Hospitals Leuven, Leuven (K.P.), and the Clinical Trials Conduct Unit (P.A.), Institut Jules Bordet-Université Libre de Bruxelles (M.J.P.), Brussels - all in Belgium; the Medical Oncology Department and Breast Cancer Group, Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology (M.O.), and the International Breast Cancer Center, Quiron Group (J.C.) - all in Barcelona; Magee-Womens Hospital and the Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh (A. Brufsky); Ohio State University Wexner Medical Center, Columbus (S.D.S.); Columbia University Irving Medical Center (K.K.) and Memorial Sloan Kettering Cancer Center (T.T.) - both in New York; Northside Hospital, Atlanta (A.B.Z.); Florida Cancer Specialists, Tampa (R.W.); Georgetown Lombardi Comprehensive Cancer Center, Washington, DC (F.L.); Rocky Mountain Cancer Centers, Greenwood Village, CO (S.D.); Baylor University Medical Center and Texas Oncology, Dallas (J.O.); Segal Cancer Centre, Jewish General Hospital, Montreal (C.F.); Barts Cancer Institute, Queen Mary University of London, London (P.S.); University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill (L.A.C.); Gianni Bonadonna Foundation, Milan (L.G.); the Department of Medicine and Research, Hämatologisch-Onkologische Gemeinschaftspraxis am Bethanien-Krankenhaus, Frankfurt, Germany (S.L.); Immunomedics, Morris Plains, NJ (D.M.G., Q.H., M.S.O., L.M.I.); and the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco (H.S.R.)
| | - Kevin Kalinsky
- From the Division of Medical Oncology, Massachusetts General Hospital Cancer Center (A. Bardia), and the Department of Medical Oncology, Dana-Farber Cancer Institute (S.M.T.) - both in Boston; the University of California, Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles (S.A.H.); the Medical Oncology Department and the Department of Drug Development and Innovation, Institut Curie, Paris (D.L.), Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse Oncopole, Toulouse (F.D.), and the Department of Medical Oncology, Centre Eugène Marquis, Rennes (V.D.) - all in France; the Department of General Medical Oncology and Multidisciplinary Breast Center, Leuven Cancer Institute, University Hospitals Leuven, Leuven (K.P.), and the Clinical Trials Conduct Unit (P.A.), Institut Jules Bordet-Université Libre de Bruxelles (M.J.P.), Brussels - all in Belgium; the Medical Oncology Department and Breast Cancer Group, Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology (M.O.), and the International Breast Cancer Center, Quiron Group (J.C.) - all in Barcelona; Magee-Womens Hospital and the Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh (A. Brufsky); Ohio State University Wexner Medical Center, Columbus (S.D.S.); Columbia University Irving Medical Center (K.K.) and Memorial Sloan Kettering Cancer Center (T.T.) - both in New York; Northside Hospital, Atlanta (A.B.Z.); Florida Cancer Specialists, Tampa (R.W.); Georgetown Lombardi Comprehensive Cancer Center, Washington, DC (F.L.); Rocky Mountain Cancer Centers, Greenwood Village, CO (S.D.); Baylor University Medical Center and Texas Oncology, Dallas (J.O.); Segal Cancer Centre, Jewish General Hospital, Montreal (C.F.); Barts Cancer Institute, Queen Mary University of London, London (P.S.); University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill (L.A.C.); Gianni Bonadonna Foundation, Milan (L.G.); the Department of Medicine and Research, Hämatologisch-Onkologische Gemeinschaftspraxis am Bethanien-Krankenhaus, Frankfurt, Germany (S.L.); Immunomedics, Morris Plains, NJ (D.M.G., Q.H., M.S.O., L.M.I.); and the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco (H.S.R.)
| | - Amelia B Zelnak
- From the Division of Medical Oncology, Massachusetts General Hospital Cancer Center (A. Bardia), and the Department of Medical Oncology, Dana-Farber Cancer Institute (S.M.T.) - both in Boston; the University of California, Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles (S.A.H.); the Medical Oncology Department and the Department of Drug Development and Innovation, Institut Curie, Paris (D.L.), Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse Oncopole, Toulouse (F.D.), and the Department of Medical Oncology, Centre Eugène Marquis, Rennes (V.D.) - all in France; the Department of General Medical Oncology and Multidisciplinary Breast Center, Leuven Cancer Institute, University Hospitals Leuven, Leuven (K.P.), and the Clinical Trials Conduct Unit (P.A.), Institut Jules Bordet-Université Libre de Bruxelles (M.J.P.), Brussels - all in Belgium; the Medical Oncology Department and Breast Cancer Group, Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology (M.O.), and the International Breast Cancer Center, Quiron Group (J.C.) - all in Barcelona; Magee-Womens Hospital and the Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh (A. Brufsky); Ohio State University Wexner Medical Center, Columbus (S.D.S.); Columbia University Irving Medical Center (K.K.) and Memorial Sloan Kettering Cancer Center (T.T.) - both in New York; Northside Hospital, Atlanta (A.B.Z.); Florida Cancer Specialists, Tampa (R.W.); Georgetown Lombardi Comprehensive Cancer Center, Washington, DC (F.L.); Rocky Mountain Cancer Centers, Greenwood Village, CO (S.D.); Baylor University Medical Center and Texas Oncology, Dallas (J.O.); Segal Cancer Centre, Jewish General Hospital, Montreal (C.F.); Barts Cancer Institute, Queen Mary University of London, London (P.S.); University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill (L.A.C.); Gianni Bonadonna Foundation, Milan (L.G.); the Department of Medicine and Research, Hämatologisch-Onkologische Gemeinschaftspraxis am Bethanien-Krankenhaus, Frankfurt, Germany (S.L.); Immunomedics, Morris Plains, NJ (D.M.G., Q.H., M.S.O., L.M.I.); and the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco (H.S.R.)
| | - Robert Weaver
- From the Division of Medical Oncology, Massachusetts General Hospital Cancer Center (A. Bardia), and the Department of Medical Oncology, Dana-Farber Cancer Institute (S.M.T.) - both in Boston; the University of California, Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles (S.A.H.); the Medical Oncology Department and the Department of Drug Development and Innovation, Institut Curie, Paris (D.L.), Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse Oncopole, Toulouse (F.D.), and the Department of Medical Oncology, Centre Eugène Marquis, Rennes (V.D.) - all in France; the Department of General Medical Oncology and Multidisciplinary Breast Center, Leuven Cancer Institute, University Hospitals Leuven, Leuven (K.P.), and the Clinical Trials Conduct Unit (P.A.), Institut Jules Bordet-Université Libre de Bruxelles (M.J.P.), Brussels - all in Belgium; the Medical Oncology Department and Breast Cancer Group, Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology (M.O.), and the International Breast Cancer Center, Quiron Group (J.C.) - all in Barcelona; Magee-Womens Hospital and the Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh (A. Brufsky); Ohio State University Wexner Medical Center, Columbus (S.D.S.); Columbia University Irving Medical Center (K.K.) and Memorial Sloan Kettering Cancer Center (T.T.) - both in New York; Northside Hospital, Atlanta (A.B.Z.); Florida Cancer Specialists, Tampa (R.W.); Georgetown Lombardi Comprehensive Cancer Center, Washington, DC (F.L.); Rocky Mountain Cancer Centers, Greenwood Village, CO (S.D.); Baylor University Medical Center and Texas Oncology, Dallas (J.O.); Segal Cancer Centre, Jewish General Hospital, Montreal (C.F.); Barts Cancer Institute, Queen Mary University of London, London (P.S.); University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill (L.A.C.); Gianni Bonadonna Foundation, Milan (L.G.); the Department of Medicine and Research, Hämatologisch-Onkologische Gemeinschaftspraxis am Bethanien-Krankenhaus, Frankfurt, Germany (S.L.); Immunomedics, Morris Plains, NJ (D.M.G., Q.H., M.S.O., L.M.I.); and the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco (H.S.R.)
| | - Tiffany Traina
- From the Division of Medical Oncology, Massachusetts General Hospital Cancer Center (A. Bardia), and the Department of Medical Oncology, Dana-Farber Cancer Institute (S.M.T.) - both in Boston; the University of California, Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles (S.A.H.); the Medical Oncology Department and the Department of Drug Development and Innovation, Institut Curie, Paris (D.L.), Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse Oncopole, Toulouse (F.D.), and the Department of Medical Oncology, Centre Eugène Marquis, Rennes (V.D.) - all in France; the Department of General Medical Oncology and Multidisciplinary Breast Center, Leuven Cancer Institute, University Hospitals Leuven, Leuven (K.P.), and the Clinical Trials Conduct Unit (P.A.), Institut Jules Bordet-Université Libre de Bruxelles (M.J.P.), Brussels - all in Belgium; the Medical Oncology Department and Breast Cancer Group, Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology (M.O.), and the International Breast Cancer Center, Quiron Group (J.C.) - all in Barcelona; Magee-Womens Hospital and the Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh (A. Brufsky); Ohio State University Wexner Medical Center, Columbus (S.D.S.); Columbia University Irving Medical Center (K.K.) and Memorial Sloan Kettering Cancer Center (T.T.) - both in New York; Northside Hospital, Atlanta (A.B.Z.); Florida Cancer Specialists, Tampa (R.W.); Georgetown Lombardi Comprehensive Cancer Center, Washington, DC (F.L.); Rocky Mountain Cancer Centers, Greenwood Village, CO (S.D.); Baylor University Medical Center and Texas Oncology, Dallas (J.O.); Segal Cancer Centre, Jewish General Hospital, Montreal (C.F.); Barts Cancer Institute, Queen Mary University of London, London (P.S.); University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill (L.A.C.); Gianni Bonadonna Foundation, Milan (L.G.); the Department of Medicine and Research, Hämatologisch-Onkologische Gemeinschaftspraxis am Bethanien-Krankenhaus, Frankfurt, Germany (S.L.); Immunomedics, Morris Plains, NJ (D.M.G., Q.H., M.S.O., L.M.I.); and the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco (H.S.R.)
| | - Florence Dalenc
- From the Division of Medical Oncology, Massachusetts General Hospital Cancer Center (A. Bardia), and the Department of Medical Oncology, Dana-Farber Cancer Institute (S.M.T.) - both in Boston; the University of California, Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles (S.A.H.); the Medical Oncology Department and the Department of Drug Development and Innovation, Institut Curie, Paris (D.L.), Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse Oncopole, Toulouse (F.D.), and the Department of Medical Oncology, Centre Eugène Marquis, Rennes (V.D.) - all in France; the Department of General Medical Oncology and Multidisciplinary Breast Center, Leuven Cancer Institute, University Hospitals Leuven, Leuven (K.P.), and the Clinical Trials Conduct Unit (P.A.), Institut Jules Bordet-Université Libre de Bruxelles (M.J.P.), Brussels - all in Belgium; the Medical Oncology Department and Breast Cancer Group, Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology (M.O.), and the International Breast Cancer Center, Quiron Group (J.C.) - all in Barcelona; Magee-Womens Hospital and the Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh (A. Brufsky); Ohio State University Wexner Medical Center, Columbus (S.D.S.); Columbia University Irving Medical Center (K.K.) and Memorial Sloan Kettering Cancer Center (T.T.) - both in New York; Northside Hospital, Atlanta (A.B.Z.); Florida Cancer Specialists, Tampa (R.W.); Georgetown Lombardi Comprehensive Cancer Center, Washington, DC (F.L.); Rocky Mountain Cancer Centers, Greenwood Village, CO (S.D.); Baylor University Medical Center and Texas Oncology, Dallas (J.O.); Segal Cancer Centre, Jewish General Hospital, Montreal (C.F.); Barts Cancer Institute, Queen Mary University of London, London (P.S.); University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill (L.A.C.); Gianni Bonadonna Foundation, Milan (L.G.); the Department of Medicine and Research, Hämatologisch-Onkologische Gemeinschaftspraxis am Bethanien-Krankenhaus, Frankfurt, Germany (S.L.); Immunomedics, Morris Plains, NJ (D.M.G., Q.H., M.S.O., L.M.I.); and the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco (H.S.R.)
| | - Philippe Aftimos
- From the Division of Medical Oncology, Massachusetts General Hospital Cancer Center (A. Bardia), and the Department of Medical Oncology, Dana-Farber Cancer Institute (S.M.T.) - both in Boston; the University of California, Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles (S.A.H.); the Medical Oncology Department and the Department of Drug Development and Innovation, Institut Curie, Paris (D.L.), Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse Oncopole, Toulouse (F.D.), and the Department of Medical Oncology, Centre Eugène Marquis, Rennes (V.D.) - all in France; the Department of General Medical Oncology and Multidisciplinary Breast Center, Leuven Cancer Institute, University Hospitals Leuven, Leuven (K.P.), and the Clinical Trials Conduct Unit (P.A.), Institut Jules Bordet-Université Libre de Bruxelles (M.J.P.), Brussels - all in Belgium; the Medical Oncology Department and Breast Cancer Group, Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology (M.O.), and the International Breast Cancer Center, Quiron Group (J.C.) - all in Barcelona; Magee-Womens Hospital and the Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh (A. Brufsky); Ohio State University Wexner Medical Center, Columbus (S.D.S.); Columbia University Irving Medical Center (K.K.) and Memorial Sloan Kettering Cancer Center (T.T.) - both in New York; Northside Hospital, Atlanta (A.B.Z.); Florida Cancer Specialists, Tampa (R.W.); Georgetown Lombardi Comprehensive Cancer Center, Washington, DC (F.L.); Rocky Mountain Cancer Centers, Greenwood Village, CO (S.D.); Baylor University Medical Center and Texas Oncology, Dallas (J.O.); Segal Cancer Centre, Jewish General Hospital, Montreal (C.F.); Barts Cancer Institute, Queen Mary University of London, London (P.S.); University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill (L.A.C.); Gianni Bonadonna Foundation, Milan (L.G.); the Department of Medicine and Research, Hämatologisch-Onkologische Gemeinschaftspraxis am Bethanien-Krankenhaus, Frankfurt, Germany (S.L.); Immunomedics, Morris Plains, NJ (D.M.G., Q.H., M.S.O., L.M.I.); and the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco (H.S.R.)
| | - Filipa Lynce
- From the Division of Medical Oncology, Massachusetts General Hospital Cancer Center (A. Bardia), and the Department of Medical Oncology, Dana-Farber Cancer Institute (S.M.T.) - both in Boston; the University of California, Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles (S.A.H.); the Medical Oncology Department and the Department of Drug Development and Innovation, Institut Curie, Paris (D.L.), Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse Oncopole, Toulouse (F.D.), and the Department of Medical Oncology, Centre Eugène Marquis, Rennes (V.D.) - all in France; the Department of General Medical Oncology and Multidisciplinary Breast Center, Leuven Cancer Institute, University Hospitals Leuven, Leuven (K.P.), and the Clinical Trials Conduct Unit (P.A.), Institut Jules Bordet-Université Libre de Bruxelles (M.J.P.), Brussels - all in Belgium; the Medical Oncology Department and Breast Cancer Group, Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology (M.O.), and the International Breast Cancer Center, Quiron Group (J.C.) - all in Barcelona; Magee-Womens Hospital and the Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh (A. Brufsky); Ohio State University Wexner Medical Center, Columbus (S.D.S.); Columbia University Irving Medical Center (K.K.) and Memorial Sloan Kettering Cancer Center (T.T.) - both in New York; Northside Hospital, Atlanta (A.B.Z.); Florida Cancer Specialists, Tampa (R.W.); Georgetown Lombardi Comprehensive Cancer Center, Washington, DC (F.L.); Rocky Mountain Cancer Centers, Greenwood Village, CO (S.D.); Baylor University Medical Center and Texas Oncology, Dallas (J.O.); Segal Cancer Centre, Jewish General Hospital, Montreal (C.F.); Barts Cancer Institute, Queen Mary University of London, London (P.S.); University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill (L.A.C.); Gianni Bonadonna Foundation, Milan (L.G.); the Department of Medicine and Research, Hämatologisch-Onkologische Gemeinschaftspraxis am Bethanien-Krankenhaus, Frankfurt, Germany (S.L.); Immunomedics, Morris Plains, NJ (D.M.G., Q.H., M.S.O., L.M.I.); and the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco (H.S.R.)
| | - Sami Diab
- From the Division of Medical Oncology, Massachusetts General Hospital Cancer Center (A. Bardia), and the Department of Medical Oncology, Dana-Farber Cancer Institute (S.M.T.) - both in Boston; the University of California, Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles (S.A.H.); the Medical Oncology Department and the Department of Drug Development and Innovation, Institut Curie, Paris (D.L.), Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse Oncopole, Toulouse (F.D.), and the Department of Medical Oncology, Centre Eugène Marquis, Rennes (V.D.) - all in France; the Department of General Medical Oncology and Multidisciplinary Breast Center, Leuven Cancer Institute, University Hospitals Leuven, Leuven (K.P.), and the Clinical Trials Conduct Unit (P.A.), Institut Jules Bordet-Université Libre de Bruxelles (M.J.P.), Brussels - all in Belgium; the Medical Oncology Department and Breast Cancer Group, Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology (M.O.), and the International Breast Cancer Center, Quiron Group (J.C.) - all in Barcelona; Magee-Womens Hospital and the Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh (A. Brufsky); Ohio State University Wexner Medical Center, Columbus (S.D.S.); Columbia University Irving Medical Center (K.K.) and Memorial Sloan Kettering Cancer Center (T.T.) - both in New York; Northside Hospital, Atlanta (A.B.Z.); Florida Cancer Specialists, Tampa (R.W.); Georgetown Lombardi Comprehensive Cancer Center, Washington, DC (F.L.); Rocky Mountain Cancer Centers, Greenwood Village, CO (S.D.); Baylor University Medical Center and Texas Oncology, Dallas (J.O.); Segal Cancer Centre, Jewish General Hospital, Montreal (C.F.); Barts Cancer Institute, Queen Mary University of London, London (P.S.); University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill (L.A.C.); Gianni Bonadonna Foundation, Milan (L.G.); the Department of Medicine and Research, Hämatologisch-Onkologische Gemeinschaftspraxis am Bethanien-Krankenhaus, Frankfurt, Germany (S.L.); Immunomedics, Morris Plains, NJ (D.M.G., Q.H., M.S.O., L.M.I.); and the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco (H.S.R.)
| | - Javier Cortés
- From the Division of Medical Oncology, Massachusetts General Hospital Cancer Center (A. Bardia), and the Department of Medical Oncology, Dana-Farber Cancer Institute (S.M.T.) - both in Boston; the University of California, Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles (S.A.H.); the Medical Oncology Department and the Department of Drug Development and Innovation, Institut Curie, Paris (D.L.), Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse Oncopole, Toulouse (F.D.), and the Department of Medical Oncology, Centre Eugène Marquis, Rennes (V.D.) - all in France; the Department of General Medical Oncology and Multidisciplinary Breast Center, Leuven Cancer Institute, University Hospitals Leuven, Leuven (K.P.), and the Clinical Trials Conduct Unit (P.A.), Institut Jules Bordet-Université Libre de Bruxelles (M.J.P.), Brussels - all in Belgium; the Medical Oncology Department and Breast Cancer Group, Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology (M.O.), and the International Breast Cancer Center, Quiron Group (J.C.) - all in Barcelona; Magee-Womens Hospital and the Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh (A. Brufsky); Ohio State University Wexner Medical Center, Columbus (S.D.S.); Columbia University Irving Medical Center (K.K.) and Memorial Sloan Kettering Cancer Center (T.T.) - both in New York; Northside Hospital, Atlanta (A.B.Z.); Florida Cancer Specialists, Tampa (R.W.); Georgetown Lombardi Comprehensive Cancer Center, Washington, DC (F.L.); Rocky Mountain Cancer Centers, Greenwood Village, CO (S.D.); Baylor University Medical Center and Texas Oncology, Dallas (J.O.); Segal Cancer Centre, Jewish General Hospital, Montreal (C.F.); Barts Cancer Institute, Queen Mary University of London, London (P.S.); University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill (L.A.C.); Gianni Bonadonna Foundation, Milan (L.G.); the Department of Medicine and Research, Hämatologisch-Onkologische Gemeinschaftspraxis am Bethanien-Krankenhaus, Frankfurt, Germany (S.L.); Immunomedics, Morris Plains, NJ (D.M.G., Q.H., M.S.O., L.M.I.); and the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco (H.S.R.)
| | - Joyce O'Shaughnessy
- From the Division of Medical Oncology, Massachusetts General Hospital Cancer Center (A. Bardia), and the Department of Medical Oncology, Dana-Farber Cancer Institute (S.M.T.) - both in Boston; the University of California, Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles (S.A.H.); the Medical Oncology Department and the Department of Drug Development and Innovation, Institut Curie, Paris (D.L.), Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse Oncopole, Toulouse (F.D.), and the Department of Medical Oncology, Centre Eugène Marquis, Rennes (V.D.) - all in France; the Department of General Medical Oncology and Multidisciplinary Breast Center, Leuven Cancer Institute, University Hospitals Leuven, Leuven (K.P.), and the Clinical Trials Conduct Unit (P.A.), Institut Jules Bordet-Université Libre de Bruxelles (M.J.P.), Brussels - all in Belgium; the Medical Oncology Department and Breast Cancer Group, Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology (M.O.), and the International Breast Cancer Center, Quiron Group (J.C.) - all in Barcelona; Magee-Womens Hospital and the Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh (A. Brufsky); Ohio State University Wexner Medical Center, Columbus (S.D.S.); Columbia University Irving Medical Center (K.K.) and Memorial Sloan Kettering Cancer Center (T.T.) - both in New York; Northside Hospital, Atlanta (A.B.Z.); Florida Cancer Specialists, Tampa (R.W.); Georgetown Lombardi Comprehensive Cancer Center, Washington, DC (F.L.); Rocky Mountain Cancer Centers, Greenwood Village, CO (S.D.); Baylor University Medical Center and Texas Oncology, Dallas (J.O.); Segal Cancer Centre, Jewish General Hospital, Montreal (C.F.); Barts Cancer Institute, Queen Mary University of London, London (P.S.); University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill (L.A.C.); Gianni Bonadonna Foundation, Milan (L.G.); the Department of Medicine and Research, Hämatologisch-Onkologische Gemeinschaftspraxis am Bethanien-Krankenhaus, Frankfurt, Germany (S.L.); Immunomedics, Morris Plains, NJ (D.M.G., Q.H., M.S.O., L.M.I.); and the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco (H.S.R.)
| | - Véronique Diéras
- From the Division of Medical Oncology, Massachusetts General Hospital Cancer Center (A. Bardia), and the Department of Medical Oncology, Dana-Farber Cancer Institute (S.M.T.) - both in Boston; the University of California, Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles (S.A.H.); the Medical Oncology Department and the Department of Drug Development and Innovation, Institut Curie, Paris (D.L.), Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse Oncopole, Toulouse (F.D.), and the Department of Medical Oncology, Centre Eugène Marquis, Rennes (V.D.) - all in France; the Department of General Medical Oncology and Multidisciplinary Breast Center, Leuven Cancer Institute, University Hospitals Leuven, Leuven (K.P.), and the Clinical Trials Conduct Unit (P.A.), Institut Jules Bordet-Université Libre de Bruxelles (M.J.P.), Brussels - all in Belgium; the Medical Oncology Department and Breast Cancer Group, Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology (M.O.), and the International Breast Cancer Center, Quiron Group (J.C.) - all in Barcelona; Magee-Womens Hospital and the Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh (A. Brufsky); Ohio State University Wexner Medical Center, Columbus (S.D.S.); Columbia University Irving Medical Center (K.K.) and Memorial Sloan Kettering Cancer Center (T.T.) - both in New York; Northside Hospital, Atlanta (A.B.Z.); Florida Cancer Specialists, Tampa (R.W.); Georgetown Lombardi Comprehensive Cancer Center, Washington, DC (F.L.); Rocky Mountain Cancer Centers, Greenwood Village, CO (S.D.); Baylor University Medical Center and Texas Oncology, Dallas (J.O.); Segal Cancer Centre, Jewish General Hospital, Montreal (C.F.); Barts Cancer Institute, Queen Mary University of London, London (P.S.); University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill (L.A.C.); Gianni Bonadonna Foundation, Milan (L.G.); the Department of Medicine and Research, Hämatologisch-Onkologische Gemeinschaftspraxis am Bethanien-Krankenhaus, Frankfurt, Germany (S.L.); Immunomedics, Morris Plains, NJ (D.M.G., Q.H., M.S.O., L.M.I.); and the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco (H.S.R.)
| | - Cristiano Ferrario
- From the Division of Medical Oncology, Massachusetts General Hospital Cancer Center (A. Bardia), and the Department of Medical Oncology, Dana-Farber Cancer Institute (S.M.T.) - both in Boston; the University of California, Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles (S.A.H.); the Medical Oncology Department and the Department of Drug Development and Innovation, Institut Curie, Paris (D.L.), Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse Oncopole, Toulouse (F.D.), and the Department of Medical Oncology, Centre Eugène Marquis, Rennes (V.D.) - all in France; the Department of General Medical Oncology and Multidisciplinary Breast Center, Leuven Cancer Institute, University Hospitals Leuven, Leuven (K.P.), and the Clinical Trials Conduct Unit (P.A.), Institut Jules Bordet-Université Libre de Bruxelles (M.J.P.), Brussels - all in Belgium; the Medical Oncology Department and Breast Cancer Group, Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology (M.O.), and the International Breast Cancer Center, Quiron Group (J.C.) - all in Barcelona; Magee-Womens Hospital and the Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh (A. Brufsky); Ohio State University Wexner Medical Center, Columbus (S.D.S.); Columbia University Irving Medical Center (K.K.) and Memorial Sloan Kettering Cancer Center (T.T.) - both in New York; Northside Hospital, Atlanta (A.B.Z.); Florida Cancer Specialists, Tampa (R.W.); Georgetown Lombardi Comprehensive Cancer Center, Washington, DC (F.L.); Rocky Mountain Cancer Centers, Greenwood Village, CO (S.D.); Baylor University Medical Center and Texas Oncology, Dallas (J.O.); Segal Cancer Centre, Jewish General Hospital, Montreal (C.F.); Barts Cancer Institute, Queen Mary University of London, London (P.S.); University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill (L.A.C.); Gianni Bonadonna Foundation, Milan (L.G.); the Department of Medicine and Research, Hämatologisch-Onkologische Gemeinschaftspraxis am Bethanien-Krankenhaus, Frankfurt, Germany (S.L.); Immunomedics, Morris Plains, NJ (D.M.G., Q.H., M.S.O., L.M.I.); and the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco (H.S.R.)
| | - Peter Schmid
- From the Division of Medical Oncology, Massachusetts General Hospital Cancer Center (A. Bardia), and the Department of Medical Oncology, Dana-Farber Cancer Institute (S.M.T.) - both in Boston; the University of California, Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles (S.A.H.); the Medical Oncology Department and the Department of Drug Development and Innovation, Institut Curie, Paris (D.L.), Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse Oncopole, Toulouse (F.D.), and the Department of Medical Oncology, Centre Eugène Marquis, Rennes (V.D.) - all in France; the Department of General Medical Oncology and Multidisciplinary Breast Center, Leuven Cancer Institute, University Hospitals Leuven, Leuven (K.P.), and the Clinical Trials Conduct Unit (P.A.), Institut Jules Bordet-Université Libre de Bruxelles (M.J.P.), Brussels - all in Belgium; the Medical Oncology Department and Breast Cancer Group, Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology (M.O.), and the International Breast Cancer Center, Quiron Group (J.C.) - all in Barcelona; Magee-Womens Hospital and the Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh (A. Brufsky); Ohio State University Wexner Medical Center, Columbus (S.D.S.); Columbia University Irving Medical Center (K.K.) and Memorial Sloan Kettering Cancer Center (T.T.) - both in New York; Northside Hospital, Atlanta (A.B.Z.); Florida Cancer Specialists, Tampa (R.W.); Georgetown Lombardi Comprehensive Cancer Center, Washington, DC (F.L.); Rocky Mountain Cancer Centers, Greenwood Village, CO (S.D.); Baylor University Medical Center and Texas Oncology, Dallas (J.O.); Segal Cancer Centre, Jewish General Hospital, Montreal (C.F.); Barts Cancer Institute, Queen Mary University of London, London (P.S.); University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill (L.A.C.); Gianni Bonadonna Foundation, Milan (L.G.); the Department of Medicine and Research, Hämatologisch-Onkologische Gemeinschaftspraxis am Bethanien-Krankenhaus, Frankfurt, Germany (S.L.); Immunomedics, Morris Plains, NJ (D.M.G., Q.H., M.S.O., L.M.I.); and the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco (H.S.R.)
| | - Lisa A Carey
- From the Division of Medical Oncology, Massachusetts General Hospital Cancer Center (A. Bardia), and the Department of Medical Oncology, Dana-Farber Cancer Institute (S.M.T.) - both in Boston; the University of California, Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles (S.A.H.); the Medical Oncology Department and the Department of Drug Development and Innovation, Institut Curie, Paris (D.L.), Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse Oncopole, Toulouse (F.D.), and the Department of Medical Oncology, Centre Eugène Marquis, Rennes (V.D.) - all in France; the Department of General Medical Oncology and Multidisciplinary Breast Center, Leuven Cancer Institute, University Hospitals Leuven, Leuven (K.P.), and the Clinical Trials Conduct Unit (P.A.), Institut Jules Bordet-Université Libre de Bruxelles (M.J.P.), Brussels - all in Belgium; the Medical Oncology Department and Breast Cancer Group, Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology (M.O.), and the International Breast Cancer Center, Quiron Group (J.C.) - all in Barcelona; Magee-Womens Hospital and the Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh (A. Brufsky); Ohio State University Wexner Medical Center, Columbus (S.D.S.); Columbia University Irving Medical Center (K.K.) and Memorial Sloan Kettering Cancer Center (T.T.) - both in New York; Northside Hospital, Atlanta (A.B.Z.); Florida Cancer Specialists, Tampa (R.W.); Georgetown Lombardi Comprehensive Cancer Center, Washington, DC (F.L.); Rocky Mountain Cancer Centers, Greenwood Village, CO (S.D.); Baylor University Medical Center and Texas Oncology, Dallas (J.O.); Segal Cancer Centre, Jewish General Hospital, Montreal (C.F.); Barts Cancer Institute, Queen Mary University of London, London (P.S.); University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill (L.A.C.); Gianni Bonadonna Foundation, Milan (L.G.); the Department of Medicine and Research, Hämatologisch-Onkologische Gemeinschaftspraxis am Bethanien-Krankenhaus, Frankfurt, Germany (S.L.); Immunomedics, Morris Plains, NJ (D.M.G., Q.H., M.S.O., L.M.I.); and the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco (H.S.R.)
| | - Luca Gianni
- From the Division of Medical Oncology, Massachusetts General Hospital Cancer Center (A. Bardia), and the Department of Medical Oncology, Dana-Farber Cancer Institute (S.M.T.) - both in Boston; the University of California, Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles (S.A.H.); the Medical Oncology Department and the Department of Drug Development and Innovation, Institut Curie, Paris (D.L.), Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse Oncopole, Toulouse (F.D.), and the Department of Medical Oncology, Centre Eugène Marquis, Rennes (V.D.) - all in France; the Department of General Medical Oncology and Multidisciplinary Breast Center, Leuven Cancer Institute, University Hospitals Leuven, Leuven (K.P.), and the Clinical Trials Conduct Unit (P.A.), Institut Jules Bordet-Université Libre de Bruxelles (M.J.P.), Brussels - all in Belgium; the Medical Oncology Department and Breast Cancer Group, Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology (M.O.), and the International Breast Cancer Center, Quiron Group (J.C.) - all in Barcelona; Magee-Womens Hospital and the Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh (A. Brufsky); Ohio State University Wexner Medical Center, Columbus (S.D.S.); Columbia University Irving Medical Center (K.K.) and Memorial Sloan Kettering Cancer Center (T.T.) - both in New York; Northside Hospital, Atlanta (A.B.Z.); Florida Cancer Specialists, Tampa (R.W.); Georgetown Lombardi Comprehensive Cancer Center, Washington, DC (F.L.); Rocky Mountain Cancer Centers, Greenwood Village, CO (S.D.); Baylor University Medical Center and Texas Oncology, Dallas (J.O.); Segal Cancer Centre, Jewish General Hospital, Montreal (C.F.); Barts Cancer Institute, Queen Mary University of London, London (P.S.); University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill (L.A.C.); Gianni Bonadonna Foundation, Milan (L.G.); the Department of Medicine and Research, Hämatologisch-Onkologische Gemeinschaftspraxis am Bethanien-Krankenhaus, Frankfurt, Germany (S.L.); Immunomedics, Morris Plains, NJ (D.M.G., Q.H., M.S.O., L.M.I.); and the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco (H.S.R.)
| | - Martine J Piccart
- From the Division of Medical Oncology, Massachusetts General Hospital Cancer Center (A. Bardia), and the Department of Medical Oncology, Dana-Farber Cancer Institute (S.M.T.) - both in Boston; the University of California, Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles (S.A.H.); the Medical Oncology Department and the Department of Drug Development and Innovation, Institut Curie, Paris (D.L.), Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse Oncopole, Toulouse (F.D.), and the Department of Medical Oncology, Centre Eugène Marquis, Rennes (V.D.) - all in France; the Department of General Medical Oncology and Multidisciplinary Breast Center, Leuven Cancer Institute, University Hospitals Leuven, Leuven (K.P.), and the Clinical Trials Conduct Unit (P.A.), Institut Jules Bordet-Université Libre de Bruxelles (M.J.P.), Brussels - all in Belgium; the Medical Oncology Department and Breast Cancer Group, Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology (M.O.), and the International Breast Cancer Center, Quiron Group (J.C.) - all in Barcelona; Magee-Womens Hospital and the Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh (A. Brufsky); Ohio State University Wexner Medical Center, Columbus (S.D.S.); Columbia University Irving Medical Center (K.K.) and Memorial Sloan Kettering Cancer Center (T.T.) - both in New York; Northside Hospital, Atlanta (A.B.Z.); Florida Cancer Specialists, Tampa (R.W.); Georgetown Lombardi Comprehensive Cancer Center, Washington, DC (F.L.); Rocky Mountain Cancer Centers, Greenwood Village, CO (S.D.); Baylor University Medical Center and Texas Oncology, Dallas (J.O.); Segal Cancer Centre, Jewish General Hospital, Montreal (C.F.); Barts Cancer Institute, Queen Mary University of London, London (P.S.); University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill (L.A.C.); Gianni Bonadonna Foundation, Milan (L.G.); the Department of Medicine and Research, Hämatologisch-Onkologische Gemeinschaftspraxis am Bethanien-Krankenhaus, Frankfurt, Germany (S.L.); Immunomedics, Morris Plains, NJ (D.M.G., Q.H., M.S.O., L.M.I.); and the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco (H.S.R.)
| | - Sibylle Loibl
- From the Division of Medical Oncology, Massachusetts General Hospital Cancer Center (A. Bardia), and the Department of Medical Oncology, Dana-Farber Cancer Institute (S.M.T.) - both in Boston; the University of California, Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles (S.A.H.); the Medical Oncology Department and the Department of Drug Development and Innovation, Institut Curie, Paris (D.L.), Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse Oncopole, Toulouse (F.D.), and the Department of Medical Oncology, Centre Eugène Marquis, Rennes (V.D.) - all in France; the Department of General Medical Oncology and Multidisciplinary Breast Center, Leuven Cancer Institute, University Hospitals Leuven, Leuven (K.P.), and the Clinical Trials Conduct Unit (P.A.), Institut Jules Bordet-Université Libre de Bruxelles (M.J.P.), Brussels - all in Belgium; the Medical Oncology Department and Breast Cancer Group, Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology (M.O.), and the International Breast Cancer Center, Quiron Group (J.C.) - all in Barcelona; Magee-Womens Hospital and the Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh (A. Brufsky); Ohio State University Wexner Medical Center, Columbus (S.D.S.); Columbia University Irving Medical Center (K.K.) and Memorial Sloan Kettering Cancer Center (T.T.) - both in New York; Northside Hospital, Atlanta (A.B.Z.); Florida Cancer Specialists, Tampa (R.W.); Georgetown Lombardi Comprehensive Cancer Center, Washington, DC (F.L.); Rocky Mountain Cancer Centers, Greenwood Village, CO (S.D.); Baylor University Medical Center and Texas Oncology, Dallas (J.O.); Segal Cancer Centre, Jewish General Hospital, Montreal (C.F.); Barts Cancer Institute, Queen Mary University of London, London (P.S.); University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill (L.A.C.); Gianni Bonadonna Foundation, Milan (L.G.); the Department of Medicine and Research, Hämatologisch-Onkologische Gemeinschaftspraxis am Bethanien-Krankenhaus, Frankfurt, Germany (S.L.); Immunomedics, Morris Plains, NJ (D.M.G., Q.H., M.S.O., L.M.I.); and the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco (H.S.R.)
| | - David M Goldenberg
- From the Division of Medical Oncology, Massachusetts General Hospital Cancer Center (A. Bardia), and the Department of Medical Oncology, Dana-Farber Cancer Institute (S.M.T.) - both in Boston; the University of California, Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles (S.A.H.); the Medical Oncology Department and the Department of Drug Development and Innovation, Institut Curie, Paris (D.L.), Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse Oncopole, Toulouse (F.D.), and the Department of Medical Oncology, Centre Eugène Marquis, Rennes (V.D.) - all in France; the Department of General Medical Oncology and Multidisciplinary Breast Center, Leuven Cancer Institute, University Hospitals Leuven, Leuven (K.P.), and the Clinical Trials Conduct Unit (P.A.), Institut Jules Bordet-Université Libre de Bruxelles (M.J.P.), Brussels - all in Belgium; the Medical Oncology Department and Breast Cancer Group, Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology (M.O.), and the International Breast Cancer Center, Quiron Group (J.C.) - all in Barcelona; Magee-Womens Hospital and the Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh (A. Brufsky); Ohio State University Wexner Medical Center, Columbus (S.D.S.); Columbia University Irving Medical Center (K.K.) and Memorial Sloan Kettering Cancer Center (T.T.) - both in New York; Northside Hospital, Atlanta (A.B.Z.); Florida Cancer Specialists, Tampa (R.W.); Georgetown Lombardi Comprehensive Cancer Center, Washington, DC (F.L.); Rocky Mountain Cancer Centers, Greenwood Village, CO (S.D.); Baylor University Medical Center and Texas Oncology, Dallas (J.O.); Segal Cancer Centre, Jewish General Hospital, Montreal (C.F.); Barts Cancer Institute, Queen Mary University of London, London (P.S.); University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill (L.A.C.); Gianni Bonadonna Foundation, Milan (L.G.); the Department of Medicine and Research, Hämatologisch-Onkologische Gemeinschaftspraxis am Bethanien-Krankenhaus, Frankfurt, Germany (S.L.); Immunomedics, Morris Plains, NJ (D.M.G., Q.H., M.S.O., L.M.I.); and the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco (H.S.R.)
| | - Quan Hong
- From the Division of Medical Oncology, Massachusetts General Hospital Cancer Center (A. Bardia), and the Department of Medical Oncology, Dana-Farber Cancer Institute (S.M.T.) - both in Boston; the University of California, Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles (S.A.H.); the Medical Oncology Department and the Department of Drug Development and Innovation, Institut Curie, Paris (D.L.), Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse Oncopole, Toulouse (F.D.), and the Department of Medical Oncology, Centre Eugène Marquis, Rennes (V.D.) - all in France; the Department of General Medical Oncology and Multidisciplinary Breast Center, Leuven Cancer Institute, University Hospitals Leuven, Leuven (K.P.), and the Clinical Trials Conduct Unit (P.A.), Institut Jules Bordet-Université Libre de Bruxelles (M.J.P.), Brussels - all in Belgium; the Medical Oncology Department and Breast Cancer Group, Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology (M.O.), and the International Breast Cancer Center, Quiron Group (J.C.) - all in Barcelona; Magee-Womens Hospital and the Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh (A. Brufsky); Ohio State University Wexner Medical Center, Columbus (S.D.S.); Columbia University Irving Medical Center (K.K.) and Memorial Sloan Kettering Cancer Center (T.T.) - both in New York; Northside Hospital, Atlanta (A.B.Z.); Florida Cancer Specialists, Tampa (R.W.); Georgetown Lombardi Comprehensive Cancer Center, Washington, DC (F.L.); Rocky Mountain Cancer Centers, Greenwood Village, CO (S.D.); Baylor University Medical Center and Texas Oncology, Dallas (J.O.); Segal Cancer Centre, Jewish General Hospital, Montreal (C.F.); Barts Cancer Institute, Queen Mary University of London, London (P.S.); University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill (L.A.C.); Gianni Bonadonna Foundation, Milan (L.G.); the Department of Medicine and Research, Hämatologisch-Onkologische Gemeinschaftspraxis am Bethanien-Krankenhaus, Frankfurt, Germany (S.L.); Immunomedics, Morris Plains, NJ (D.M.G., Q.H., M.S.O., L.M.I.); and the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco (H.S.R.)
| | - Martin S Olivo
- From the Division of Medical Oncology, Massachusetts General Hospital Cancer Center (A. Bardia), and the Department of Medical Oncology, Dana-Farber Cancer Institute (S.M.T.) - both in Boston; the University of California, Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles (S.A.H.); the Medical Oncology Department and the Department of Drug Development and Innovation, Institut Curie, Paris (D.L.), Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse Oncopole, Toulouse (F.D.), and the Department of Medical Oncology, Centre Eugène Marquis, Rennes (V.D.) - all in France; the Department of General Medical Oncology and Multidisciplinary Breast Center, Leuven Cancer Institute, University Hospitals Leuven, Leuven (K.P.), and the Clinical Trials Conduct Unit (P.A.), Institut Jules Bordet-Université Libre de Bruxelles (M.J.P.), Brussels - all in Belgium; the Medical Oncology Department and Breast Cancer Group, Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology (M.O.), and the International Breast Cancer Center, Quiron Group (J.C.) - all in Barcelona; Magee-Womens Hospital and the Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh (A. Brufsky); Ohio State University Wexner Medical Center, Columbus (S.D.S.); Columbia University Irving Medical Center (K.K.) and Memorial Sloan Kettering Cancer Center (T.T.) - both in New York; Northside Hospital, Atlanta (A.B.Z.); Florida Cancer Specialists, Tampa (R.W.); Georgetown Lombardi Comprehensive Cancer Center, Washington, DC (F.L.); Rocky Mountain Cancer Centers, Greenwood Village, CO (S.D.); Baylor University Medical Center and Texas Oncology, Dallas (J.O.); Segal Cancer Centre, Jewish General Hospital, Montreal (C.F.); Barts Cancer Institute, Queen Mary University of London, London (P.S.); University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill (L.A.C.); Gianni Bonadonna Foundation, Milan (L.G.); the Department of Medicine and Research, Hämatologisch-Onkologische Gemeinschaftspraxis am Bethanien-Krankenhaus, Frankfurt, Germany (S.L.); Immunomedics, Morris Plains, NJ (D.M.G., Q.H., M.S.O., L.M.I.); and the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco (H.S.R.)
| | - Loretta M Itri
- From the Division of Medical Oncology, Massachusetts General Hospital Cancer Center (A. Bardia), and the Department of Medical Oncology, Dana-Farber Cancer Institute (S.M.T.) - both in Boston; the University of California, Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles (S.A.H.); the Medical Oncology Department and the Department of Drug Development and Innovation, Institut Curie, Paris (D.L.), Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse Oncopole, Toulouse (F.D.), and the Department of Medical Oncology, Centre Eugène Marquis, Rennes (V.D.) - all in France; the Department of General Medical Oncology and Multidisciplinary Breast Center, Leuven Cancer Institute, University Hospitals Leuven, Leuven (K.P.), and the Clinical Trials Conduct Unit (P.A.), Institut Jules Bordet-Université Libre de Bruxelles (M.J.P.), Brussels - all in Belgium; the Medical Oncology Department and Breast Cancer Group, Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology (M.O.), and the International Breast Cancer Center, Quiron Group (J.C.) - all in Barcelona; Magee-Womens Hospital and the Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh (A. Brufsky); Ohio State University Wexner Medical Center, Columbus (S.D.S.); Columbia University Irving Medical Center (K.K.) and Memorial Sloan Kettering Cancer Center (T.T.) - both in New York; Northside Hospital, Atlanta (A.B.Z.); Florida Cancer Specialists, Tampa (R.W.); Georgetown Lombardi Comprehensive Cancer Center, Washington, DC (F.L.); Rocky Mountain Cancer Centers, Greenwood Village, CO (S.D.); Baylor University Medical Center and Texas Oncology, Dallas (J.O.); Segal Cancer Centre, Jewish General Hospital, Montreal (C.F.); Barts Cancer Institute, Queen Mary University of London, London (P.S.); University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill (L.A.C.); Gianni Bonadonna Foundation, Milan (L.G.); the Department of Medicine and Research, Hämatologisch-Onkologische Gemeinschaftspraxis am Bethanien-Krankenhaus, Frankfurt, Germany (S.L.); Immunomedics, Morris Plains, NJ (D.M.G., Q.H., M.S.O., L.M.I.); and the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco (H.S.R.)
| | - Hope S Rugo
- From the Division of Medical Oncology, Massachusetts General Hospital Cancer Center (A. Bardia), and the Department of Medical Oncology, Dana-Farber Cancer Institute (S.M.T.) - both in Boston; the University of California, Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles (S.A.H.); the Medical Oncology Department and the Department of Drug Development and Innovation, Institut Curie, Paris (D.L.), Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse Oncopole, Toulouse (F.D.), and the Department of Medical Oncology, Centre Eugène Marquis, Rennes (V.D.) - all in France; the Department of General Medical Oncology and Multidisciplinary Breast Center, Leuven Cancer Institute, University Hospitals Leuven, Leuven (K.P.), and the Clinical Trials Conduct Unit (P.A.), Institut Jules Bordet-Université Libre de Bruxelles (M.J.P.), Brussels - all in Belgium; the Medical Oncology Department and Breast Cancer Group, Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology (M.O.), and the International Breast Cancer Center, Quiron Group (J.C.) - all in Barcelona; Magee-Womens Hospital and the Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh (A. Brufsky); Ohio State University Wexner Medical Center, Columbus (S.D.S.); Columbia University Irving Medical Center (K.K.) and Memorial Sloan Kettering Cancer Center (T.T.) - both in New York; Northside Hospital, Atlanta (A.B.Z.); Florida Cancer Specialists, Tampa (R.W.); Georgetown Lombardi Comprehensive Cancer Center, Washington, DC (F.L.); Rocky Mountain Cancer Centers, Greenwood Village, CO (S.D.); Baylor University Medical Center and Texas Oncology, Dallas (J.O.); Segal Cancer Centre, Jewish General Hospital, Montreal (C.F.); Barts Cancer Institute, Queen Mary University of London, London (P.S.); University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill (L.A.C.); Gianni Bonadonna Foundation, Milan (L.G.); the Department of Medicine and Research, Hämatologisch-Onkologische Gemeinschaftspraxis am Bethanien-Krankenhaus, Frankfurt, Germany (S.L.); Immunomedics, Morris Plains, NJ (D.M.G., Q.H., M.S.O., L.M.I.); and the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco (H.S.R.)
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Hall PE, Schmid P. Emerging drugs for the treatment of triple-negative breast cancer: a focus on phase II immunotherapy trials. Expert Opin Emerg Drugs 2021; 26:131-147. [PMID: 33870839 DOI: 10.1080/14728214.2021.1916468] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Introduction: Triple-negative breast cancer accounts for 10-20% of invasive breast cancers and is characterized by an aggressive phenotype and poor outcomes in the early and advanced settings compared to other breast cancer subtypes. Chemotherapy continues to be the mainstay of treatment, but recent advances have demonstrated the benefit of adding immune checkpoint inhibitors (ICIs) to chemotherapy regimens for patients with both early and advanced TNBC, particularly if PD-L1-positive. Despite these results, further improvements are needed.Areas covered: This review covers immunotherapy drugs which have recently completed, involved in ongoing or due to start phase II trials. This includes approaches to augment the response to existing ICIs, next-generation ICIs, combination treatments with targeted agents and drugs that target the tumor microenvironment. Potential development issues are also discussed.Expert opinion: The field of immunotherapy is developing rapidly and holds great promise for patients with TNBC. Promising avenues of research currently in phase II trials include targeting multiple immune checkpoints simultaneously and the addition of phosphatidylinositol 3-kinase (PI3K)/AKT inhibitors to ICI/chemotherapy regimens. A better understanding of the immunosuppressive role played by the tumor microenvironment has also been important. However, challenges remain, particularly regarding the need for more effective predictive biomarkers.
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Affiliation(s)
- Peter E Hall
- Dept. Of Medical Oncology, Barts Health NHS Trust, London, UK
| | - Peter Schmid
- Dept. Of Medical Oncology, Barts Health NHS Trust, London, UK.,Barts Cancer Institute, Queen Mary University of London, London, UK
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Chan A, Lomma C, Chih H, Blackely E, Woodward N, Tsoi D, Cheong K, Chipman M, Redfern A. Incorporation of eribulin in the systemic treatment of metastatic breast cancer patients in Australia. Asia Pac J Clin Oncol 2021; 18:201-208. [PMID: 33855786 DOI: 10.1111/ajco.13576] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Accepted: 02/05/2021] [Indexed: 01/02/2023]
Abstract
PURPOSE Review of utilization and efficacy of eribulin in Australian metastatic breast cancer (MBC) patients. METHODS Retrospective review of consecutive MBC patients treated with eribulin in tertiary Australian BC centers. Key inclusion criteria included eribulin administration in nonclinical trial setting from October 2014 onwards, known duration of MBC systemic treatments administered and known follow-up date after eribulin. Cox regression model was used to assess survival. RESULTS Study population comprised 266 patients from eight centers treated between October 2014 and May 2018. Median age at time of MBC diagnosis was 54 years with 18% of patients having de novo MBC. Seventy-six percent had hormone receptor positive (HRp) disease, 19% triple negative (TN) and 5% HER2-positive. CNS involvement was present in 36% of patients. Eribulin was most frequently given as third-line chemotherapy (36%), with no prior anthracycline exposure in 14% of total population. Eribulin was given more frequently as ≤third-line chemotherapy than > third-line in patients with TN disease, ≥ two metastatic sites or CNS disease. Median overall survival (OS) from eribulin administration was 9.2 (95% CI [8.0, 10.3]) months. CONCLUSION Similar efficacy was demonstrated for eribulin when given in the first-line to beyond the fifth line of chemotherapy in all subtypes of MBC.
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Affiliation(s)
- Arlene Chan
- Breast Cancer Research Centre-WA and Curtin University, Perth, Western Australia, Australia
| | - Christopher Lomma
- Breast Cancer Research Centre-WA, Perth, Western Australia, Australia
| | - HuiJun Chih
- School of Public Health, Curtin University, Bentley, Perth, Western Australia, Australia
| | | | - Natasha Woodward
- Mater Misericordiae Ltd/ University of Queensland, Brisbane, Queensland, Australia
| | - Daphne Tsoi
- St John of God Hospital - Subiaco and Murdoch, Western Australia, Australia
| | - Kerry Cheong
- Ashford Cancer Centre Research, Adelaide, Southern Australia, Australia
| | - Mitchell Chipman
- "Victorian Breast and Oncology Care" at St Vincent's Private Hospital, East Melbourne, Victoria, Australia
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Krasniqi E, Pizzuti L, Valerio MR, Capomolla E, Botti C, Sanguineti G, Marchetti P, Anselmi E, Tomao S, Giordano A, Ficorella C, Cannita K, Livi L, Meattini I, Mauri M, Greco F, Veltri EM, Michelotti A, Moscetti L, Giotta F, Lorusso V, Paris I, Tomao F, Santini D, Tonini G, Villa A, Gebbia V, Gamucci T, Ciliberto G, Sperduti I, Mazzotta M, Barba M, Vici P. Second-line Eribulin in Triple Negative Metastatic Breast Cancer patients. Multicentre Retrospective Study: The TETRIS Trial. Int J Med Sci 2021; 18:2245-2250. [PMID: 33859534 PMCID: PMC8040412 DOI: 10.7150/ijms.54996] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2020] [Accepted: 12/18/2020] [Indexed: 12/31/2022] Open
Abstract
Introduction: Large and consistent evidence supports the use of eribulin mesylate in clinical practice in third or later line treatment of metastatic triple negative breast cancer (mTNBC). Conversely, there is paucity of data on eribulin efficacy in second line treatment. Methods: We investigated outcomes of 44 mTNBC patients treated from 2013 through 2019 with second line eribulin mesylate in a multicentre retrospective study involving 14 Italian oncologic centres. Results: Median age was 51 years, with 11.4% of these patients being metastatic at diagnosis. Median overall survival (OS) and progression free survival (PFS) from eribulin starting were 11.9 (95%CI: 8.4-15.5) and 3.5 months (95%CI: 1.7-5.3), respectively. We observed 8 (18.2%) partial responses and 10 (22.7%) patients had stable disease as best response. A longer PFS on previous first line treatment predicted a better OS (HR=0.87, 95%CI: 0.77-0.99, p= 0.038) and a longer PFS on eribulin treatment (HR=0.92, 95%CI: 0.85-0.98, p=0.018). Progression free survival to eribulin was also favorably influenced by prior adjuvant chemotherapy (HR=0.44, 95%CI: 0.22-0.88, p=0.02). Eribulin was generally well tolerated, with grade 3-4 adverse events being recorded in 15.9% of patients. Conclusions: The outcomes described for our cohort are consistent with those reported in the pivotal Study301 and subsequent observational studies. Further data from adequately-sized, ad hoc trials on eribulin use in second line for mTNBC are warranted to confirm our findings.
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Affiliation(s)
- Eriseld Krasniqi
- Division of Medical Oncology 2, IRCCS Regina Elena National Cancer Institute, Rome, Italy
| | - Laura Pizzuti
- Division of Medical Oncology 2, IRCCS Regina Elena National Cancer Institute, Rome, Italy
| | - Maria Rosaria Valerio
- Department of Surgical, Oncological and Oral Sciences, Medical Oncology Unit, University of Palermo, Italy
| | - Elisabetta Capomolla
- Division of Medical Oncology 2, IRCCS Regina Elena National Cancer Institute, Rome, Italy
| | - Claudio Botti
- Department of Surgery, IRCCS Regina Elena National Cancer Institute, Rome, Italy
| | - Giuseppe Sanguineti
- Department of Radiation Oncology, IRCCS Regina Elena National Cancer Institute, Rome, Italy
| | - Paolo Marchetti
- Medical Oncology Unit B, Policlinico Umberto I, Rome, Italy
- Medical Oncology Unit, Azienda Ospedaliera Universitaria Sant'Andrea, Rome, Italy
| | - Elisabetta Anselmi
- Medical Oncology Unit, Azienda Ospedaliera Universitaria Sant'Andrea, Rome, Italy
| | - Silverio Tomao
- Department of Radiological, Oncological and Anatomo-Pathological Sciences, 'Sapienza' University of Rome, Policlinico Umberto I, Rome, Italy
| | - Antonio Giordano
- Sbarro Institute for Cancer Research and Molecular Medicine and Center of Biotechnology, College of Science and Technology, Temple University, Philadelphia, Pennsylvania, USA
| | - Corrado Ficorella
- Medical Oncology, Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy
| | - Katia Cannita
- Medical Oncology, St. Salvatore Hospital, L'Aquila, Italy
| | - Lorenzo Livi
- Radiation Oncology Unit and Department of Clinical and Experimental Biomedical Sciences “Mario Serio”, Azienda Ospedaliera Universitaria Careggi, University of Florence, Florence, Italy
| | - Icro Meattini
- Radiation Oncology Unit and Department of Clinical and Experimental Biomedical Sciences “Mario Serio”, Azienda Ospedaliera Universitaria Careggi, University of Florence, Florence, Italy
| | - Maria Mauri
- Division of Oncology, San Giovanni Addolorata Hospital, Rome, Italy
| | - Filippo Greco
- Department of Pathology, Surgery and Oncology, “Mater Salutis” Hospital, ULSS21, Verona, Italy
| | | | - Andrea Michelotti
- UO Oncologia Medica I, S. Chiara Hospital, Dipartimento di Oncologia, Dei Trapianti e Delle Nuove Tecnologie, Azienda Ospedaliera Universitaria Pisana, Pisa, Italy
| | - Luca Moscetti
- Division of Medical Oncology, Department of Oncology and Hematology, University Hospital of Modena, Modena, Italy
| | - Francesco Giotta
- Department of Medical Oncology, “Giovanni Paolo II” Institute, Bari, Italy
| | - Vito Lorusso
- Department of Medical Oncology, “Giovanni Paolo II” Institute, Bari, Italy
| | - Ida Paris
- Gynecology Oncology Unit, Catholic University of the Sacred Heart, Rome, Italy
| | - Federica Tomao
- Department of Gynecology-Obstetrics and Urology, “Sapienza” University of Rome, Rome, Italy
| | - Daniele Santini
- Department of Oncology, University Campus Biomedico of Rome, Rome, Italy
| | - Giuseppe Tonini
- Department of Oncology, University Campus Biomedico of Rome, Rome, Italy
| | - Alice Villa
- Department of Medical Oncology, Policlinico Universitario “A. Gemelli”, Rome, Italy
| | - Vittorio Gebbia
- Medical Oncology, La Maddalena Nursing Home, University of Palermo, Palermo, Italy
| | - Teresa Gamucci
- Medical Oncology Unit, Sandro Pertini Hospital, Rome, Italy
| | - Gennaro Ciliberto
- Scientific Direction, IRCCS Regina Elena National Cancer Institute, Rome, Italy
| | - Isabella Sperduti
- Bio-Statistics Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy
| | - Marco Mazzotta
- Division of Medical Oncology 2, IRCCS Regina Elena National Cancer Institute, Rome, Italy
| | - Maddalena Barba
- Division of Medical Oncology 2, IRCCS Regina Elena National Cancer Institute, Rome, Italy
| | - Patrizia Vici
- Division of Medical Oncology 2, IRCCS Regina Elena National Cancer Institute, Rome, Italy
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Sabatier R, Martin J, Vicier C, Guérin M, Monneur A, Provansal M, Tassy L, Tarpin C, Extra JM, Viret F, Goncalves A. Eribulin Efficacy on Brain Metastases in Heavily Pretreated Patients with Metastatic Breast Cancer. J Clin Med 2021; 10:jcm10061272. [PMID: 33803894 PMCID: PMC8003126 DOI: 10.3390/jcm10061272] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 03/09/2021] [Accepted: 03/13/2021] [Indexed: 01/15/2023] Open
Abstract
The onset of brain metastases (BM) is a major turning point during advanced breast cancer (ABC) evolution, with only few treatment options when local therapies have failed. The therapeutic effect of eribulin, a wildly used drug in the treatment of ABC, remains unclear in this setting. Patients and Methods: We performed a retrospective observational study to assess eribulin efficacy in patients with ABC who displayed BM at time of eribulin initiation. We collected data from the medical files of all ABC patients who received eribulin at our institution from 2012 until 2020. Our main endpoint was the central nervous system (CNS) progression-free survival. (CNS-PFS). Other evaluation criteria were extra-cranial progression free survival (PFS) and overall survival (OS). Results: Twenty patients with BM monitoring data available were selected out of the 549 who received eribulin during the inclusion period. Fifteen patients (75%) had BM progressive as the best response, three patients (15%) had disease stabilization for more than 6 months and only one patient had a partial response according to RECIST 1.1 criteria. Median CNS-PFS was 3.39 months (95CI (3.02–3.76)). Cox univariate analysis identified molecular subtype as the only prognostic parameter in our cohort, with patients with hormone-receptor positive tumors less likely to experience CNS progression than those with triple-negative MBC (HR = 0.23 (95CI = 0.07–0.80), p = 0.021). Median extra-cranial PFS was 2.67 months (95CI (2.33–3.01)). Median OS was 7.68 months (95CI (0–17.41)). Conclusion: Eribulin seems to have only a limited impact on BM evolution. Hormone receptors expression may identify a subset of patients with better BM control.
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Affiliation(s)
- Renaud Sabatier
- Department of Medical Oncology, Institut Paoli-Calmettes, 13009 Marseille, France; (J.M.); (C.V.); (M.G.); (A.M.); (M.P.); (L.T.); (C.T.); (J.-M.E.); (F.V.); (A.G.)
- Aix-Marseille Univ, CNRS U7258, INSERM U1068, Institut Paoli-Calmettes, CRCM, 13009 Marseille, France
- Correspondence:
| | - Johan Martin
- Department of Medical Oncology, Institut Paoli-Calmettes, 13009 Marseille, France; (J.M.); (C.V.); (M.G.); (A.M.); (M.P.); (L.T.); (C.T.); (J.-M.E.); (F.V.); (A.G.)
- Aix-Marseille Univ, CNRS U7258, INSERM U1068, Institut Paoli-Calmettes, CRCM, 13009 Marseille, France
| | - Cécile Vicier
- Department of Medical Oncology, Institut Paoli-Calmettes, 13009 Marseille, France; (J.M.); (C.V.); (M.G.); (A.M.); (M.P.); (L.T.); (C.T.); (J.-M.E.); (F.V.); (A.G.)
| | - Mathilde Guérin
- Department of Medical Oncology, Institut Paoli-Calmettes, 13009 Marseille, France; (J.M.); (C.V.); (M.G.); (A.M.); (M.P.); (L.T.); (C.T.); (J.-M.E.); (F.V.); (A.G.)
| | - Audrey Monneur
- Department of Medical Oncology, Institut Paoli-Calmettes, 13009 Marseille, France; (J.M.); (C.V.); (M.G.); (A.M.); (M.P.); (L.T.); (C.T.); (J.-M.E.); (F.V.); (A.G.)
| | - Magali Provansal
- Department of Medical Oncology, Institut Paoli-Calmettes, 13009 Marseille, France; (J.M.); (C.V.); (M.G.); (A.M.); (M.P.); (L.T.); (C.T.); (J.-M.E.); (F.V.); (A.G.)
| | - Louis Tassy
- Department of Medical Oncology, Institut Paoli-Calmettes, 13009 Marseille, France; (J.M.); (C.V.); (M.G.); (A.M.); (M.P.); (L.T.); (C.T.); (J.-M.E.); (F.V.); (A.G.)
| | - Carole Tarpin
- Department of Medical Oncology, Institut Paoli-Calmettes, 13009 Marseille, France; (J.M.); (C.V.); (M.G.); (A.M.); (M.P.); (L.T.); (C.T.); (J.-M.E.); (F.V.); (A.G.)
| | - Jean-Marc Extra
- Department of Medical Oncology, Institut Paoli-Calmettes, 13009 Marseille, France; (J.M.); (C.V.); (M.G.); (A.M.); (M.P.); (L.T.); (C.T.); (J.-M.E.); (F.V.); (A.G.)
| | - Frédéric Viret
- Department of Medical Oncology, Institut Paoli-Calmettes, 13009 Marseille, France; (J.M.); (C.V.); (M.G.); (A.M.); (M.P.); (L.T.); (C.T.); (J.-M.E.); (F.V.); (A.G.)
| | - Anthony Goncalves
- Department of Medical Oncology, Institut Paoli-Calmettes, 13009 Marseille, France; (J.M.); (C.V.); (M.G.); (A.M.); (M.P.); (L.T.); (C.T.); (J.-M.E.); (F.V.); (A.G.)
- Aix-Marseille Univ, CNRS U7258, INSERM U1068, Institut Paoli-Calmettes, CRCM, 13009 Marseille, France
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Yuan P, Xu B. Clinical Utility of Eribulin Mesylate in the Treatment of Breast Cancer: A Chinese Perspective. BREAST CANCER-TARGETS AND THERAPY 2021; 13:135-150. [PMID: 33658845 PMCID: PMC7917473 DOI: 10.2147/bctt.s231298] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/16/2020] [Accepted: 01/12/2021] [Indexed: 12/23/2022]
Abstract
Eribulin mesylate, a synthetic derivative of the anti-mitotic agent halichondrin B, has a unique tubulin-based mechanism of action that is distinct from other anti-microtubule agents including taxanes and vinca alkaloids. Consistent with this unique activity, eribulin has shown clinical efficacy in patients with metastatic breast cancer (MBC) that progressed following prior taxane and anthracycline therapy. The evidence presented in this review indicates that eribulin represents a treatment option for patients with HER2-negative metastatic breast cancer. Improved survival outcomes and better tolerability compared with vinorelbine supported the first approval of eribulin in China in 2019; eribulin was approved for women with locally advanced/metastatic HER2-negative breast cancer after treatment failure with at least two chemotherapy regimens, including an anthracycline and a taxane. Eribulin has also shown promising efficacy in patients with HER2-positive advanced breast cancer when used in combination with trastuzumab or pertuzumab, and subgroup analyses from the Phase III clinical trials support the continued evaluation of eribulin in patients with triple-negative disease. The unique non-mitotic effects of eribulin, including vascular remodeling, coupled with its clinical efficacy and safety profile, may permit the broader use of this agent in patients with MBC.
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Affiliation(s)
- Peng Yuan
- National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People's Republic of China
| | - Binghe Xu
- National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People's Republic of China
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Valerio MR, Arrivas Bajardi E, Arcara CC, Borsellino N, Lo Mauro M, Cipolla C, Santarpia M, Firenze A, Motta G, Vigneri P, Gebbia V. Eribulin Mesylate for the Treatment of Metastatic Hormone-refractory and Triple-negative Breast Cancer: A Multi-institutional Real-world Report on Efficacy and Safety. Am J Clin Oncol 2021; 44:105-108. [PMID: 33481372 DOI: 10.1097/coc.0000000000000790] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
OBJECTIVE Eribulin mesylate (EM) is a fully synthetic macrocyclic ketone analogue of the marine natural product halichondrin. EM has been reported to be active in metastatic breast cancer. In this paper, we report efficacy and safety of data of EM in a retrospective, real-world series of patients with poor prognosis, hormone-refractory, or triple-negative metastatic breast cancer. MATERIALS AND METHODS The analysis was carried out at 4 interrelated oncology centers. EM was delivered at the dose of 1.4 mg/m2 in 100 mL of normal saline over 2 to 5 minutes on days 1 and 8 every 21 days. EM was continued until disease progression or unacceptable toxicity. Side effects were reported every cycle as per standard clinical practice and graded according to NCI-CTCAE, version 4.0. Time-to-progression and overall survival were reported. RESULTS In this series of 90 patients the overall response rate was 22%, and 21% and 23% in the hormonal-resistant group and the triple-negative one, respectively. Stable disease was recorded in 24%, 21%, and 27%, respectively, in the whole series, the hormonal-resistant group, and the triple-negative one, respectively. Time-to-progression was 3.5 months (range, 1 to 22 mo) in the whole series and 3.0 months (range, 1 to 14.7 mo) and 3.4 months (range, 2.2 to 16.2 mo) in the hormonal-resistant group and the triple-negative one, respectively. Overall survival reached a median of 11.4 months. CONCLUSIONS This multicenter study, albeit retrospective, demonstrates the activity of this combination as third-line chemotherapy option in a challenging clinical setting such as triple-negative or hormone-resistant patients with breast cancer progressing after several lines of hormonal manipulations.
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Affiliation(s)
| | | | | | | | | | | | - Mariacarmela Santarpia
- Medical Oncology Unit, Department of Human Pathology "G. Barresi," University of Messina, Messina
| | | | | | | | - Vittorio Gebbia
- Oncology Section, Department "Promise," University of Palermo
- Medical Oncology Unit, La Maddalena Clinic for Cancer
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A transposon screen identifies enhancement of NF-κB pathway as a mechanism of resistance to eribulin. Breast Cancer 2021; 28:884-895. [PMID: 33616862 DOI: 10.1007/s12282-021-01224-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2020] [Accepted: 02/07/2021] [Indexed: 01/24/2023]
Abstract
BACKGROUND Eribulin mesylate (eribulin) is an efficient microtubule inhibitor that is used for metastatic breast cancer. However, breast cancer can develop resistance to eribulin. This resistance mechanism needs to be elucidated. METHODS A transposon mutagenesis screen was conducted using a pPB-SB-CMV-puro-SD plasmid and pCMV-PBase transposase. Viability and cytotoxicity were analyzed by MTT assay and flow cytometry, respectively. Real-time PCR and western blot were used for gene expression analysis. In addition, vivo study was also designed to analyze therapy efficiency. RESULTS TAB2, which is part of the nuclear factor-kappa B (NF-κB) pathway, was identified as a candidate eribulin-resistant gene. TAB2 down-regulation resulted in significantly lower cell viability and higher cytotoxicity of cells treated with eribulin, while TAB2 up-regulation showed opposite results. Similarly, combination of NF-κB inhibitors [Bay-117082 and QNZ (quinazoline derivative)] with eribulin showed significantly lower cell viability and higher drug cytotoxicity than single agent treatment with eribulin in MDA-MB-231 cells. However, QNZ increased NF-κB activity in MCF7 cells by up-regulating TAB2, which reduced the sensitivity to eribulin. Furthermore, combination of Bay-117082 with eribulin induced greater regression of MDA-MB-231 tumors compared to eribulin monotherapy in vivo. CONCLUSIONS These results consistently illustrated that TAB2-NF-κB pathway may increases resistance to eribulin in breast cancer models. Moreover, these results support the use of a combination strategy of eribulin with NF-κB inhibitors, and provide evidence that transposon mutagenesis screens are capable of identifying drug-resistant genes.
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Pellegrino B, Cavanna L, Boggiani D, Zamagni C, Frassoldati A, Schirone A, Caldara A, Rocca A, Gori S, Piacentini F, Berardi R, Brandes AA, Foglietta J, Villa F, Todeschini R, Tognetto M, Naldi N, Bortesi B, Montemurro F, Ardizzoni A, Boni L, Musolino A. Phase II study of eribulin in combination with gemcitabine for the treatment of patients with locally advanced or metastatic triple negative breast cancer (ERIGE trial). Clinical and pharmacogenetic results on behalf of the Gruppo Oncologico Italiano di Ricerca Clinica (GOIRC). ESMO Open 2021; 6:100019. [PMID: 33399082 PMCID: PMC7808100 DOI: 10.1016/j.esmoop.2020.100019] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2020] [Revised: 11/07/2020] [Accepted: 11/17/2020] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND The combination of a microtubule inhibitor (eribulin) with a nucleoside analog (gemcitabine) may synergistically induce tumor cell death, particularly in triple negative breast cancer (TNBC) characterized by high cell proliferation, aggressive behavior, and chemo-resistance. PATIENTS AND METHODS This is an open-label, multicenter phase II study evaluating the combination of eribulin (0.88 mg/m2) plus gemcitabine (1000 mg/m2) on days 1 and 8 of a 21-day cycle as either first- or second-line treatment of locally advanced or metastatic TNBC. The primary endpoint was the objective response for evaluable patients. A prospective, molecular correlative study was carried out to assess the role of germinal BRCA pathogenic variants and single nucleotide polymorphisms (SNPs) in predicting efficacy and toxicity of the combination regimen. RESULTS From July 2013 to September 2016, 83 evaluable patients were enrolled. They received a median number of six cycles of treatment. An overall response rate (ORR) of 37.3% (31 patients) was observed, with a complete response rate of 2.4% and a partial response rate of 34.9%; the clinical benefit rate was 48.8%. With a median follow-up of 28.8 months, the median response duration was 6.6 months, the median progression-free survival (PFS) was 5.1 months, and the median overall survival (OS) was 14.5 months. The most common grade 3-4 adverse events were aminotransferase elevation (in 25% of the patients) and neutropenia (in 23.8%). Women with BRCA1/2 pathogenic variants were associated with worse ORR, PFS, and OS than BRCA1/2 wild-type carriers. CYP3A4 and FGD4 SNPs were associated with increased risk of liver toxicity. Three different SNPs in CDA∗2, RRM1, and CYP2C8 genes were significantly associated with poorer OS. CONCLUSIONS The combination of eribulin and gemcitabine showed promising activity and a moderate toxicity profile in metastatic TNBC. BRCA status and pharmacogenetics tests may help identify patients with high probability of response with negligible toxicity. EUDRACT NUMBER 2012-003505-10.
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Affiliation(s)
- B Pellegrino
- Medical Oncology and Breast Unit, University Hospital of Parma, Parma, Italy; Italian Oncology Group for Clinical Research (GOIRC), Parma, Italy; Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - L Cavanna
- Hospital of Piacenza, Piacenza, Italy
| | - D Boggiani
- Medical Oncology and Breast Unit, University Hospital of Parma, Parma, Italy; Italian Oncology Group for Clinical Research (GOIRC), Parma, Italy
| | - C Zamagni
- SSD Oncologia Medica Addarii, Policlinico S.Orsola-Malpighi, Bologna, Italy
| | - A Frassoldati
- Italian Oncology Group for Clinical Research (GOIRC), Parma, Italy; Medical Oncology Unit, University Hospital of Ferrara, Ferrara, Italy
| | - A Schirone
- Medical Oncology Unit, University Hospital of Ferrara, Ferrara, Italy
| | - A Caldara
- Medical Oncology Unit, Ospedale Santa Chiara, Trento, Italy
| | - A Rocca
- Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola (FC), Italy
| | - S Gori
- Sacro Cuore-Don Calabria Hospital, Negrar (VR), Italy
| | - F Piacentini
- Medical Oncology Unit, University Hospital of Modena, Modena, Italy
| | - R Berardi
- Ancona University Hospital, Ancona, Italy
| | - A A Brandes
- Department of Medical Oncology, Azienda USL, Bologna, Italy
| | | | - F Villa
- Hospital of Lecco, Lecco, Italy
| | - R Todeschini
- Italian Oncology Group for Clinical Research (GOIRC), Parma, Italy
| | - M Tognetto
- Oncologia Medica, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - N Naldi
- Medical Oncology and Breast Unit, University Hospital of Parma, Parma, Italy
| | - B Bortesi
- Medical Oncology and Breast Unit, University Hospital of Parma, Parma, Italy
| | - F Montemurro
- Multidisciplinary Oncology Outpatient Clinic, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Italy
| | - A Ardizzoni
- Oncologia Medica, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - L Boni
- Clinical Epidemiology Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - A Musolino
- Medical Oncology and Breast Unit, University Hospital of Parma, Parma, Italy; Italian Oncology Group for Clinical Research (GOIRC), Parma, Italy; Department of Medicine and Surgery, University of Parma, Parma, Italy.
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McGuinness JE, Kalinsky K. Antibody-drug conjugates in metastatic triple negative breast cancer: a spotlight on sacituzumab govitecan, ladiratuzumab vedotin, and trastuzumab deruxtecan. Expert Opin Biol Ther 2020; 21:903-913. [PMID: 33089726 DOI: 10.1080/14712598.2021.1840547] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
INTRODUCTION Metastatic triple-negative breast cancers (mTNBC) are characterized by aggressive behavior and worse clinical outcomes than other breast cancer subtypes, as well as poor response to cytotoxic chemotherapies. The use of antibody-drug conjugates (ADCs) has been investigated as a potential treatment strategy, particularly in heavily pretreated disease. AREAS COVERED This article reviews the preclinical and clinical data supporting the use of the ADCs sacituzumab govitecan (SG), ladiratuzumab vedotin (LV), and trastuzumab deruxtecan (T-DXd) in mTNBC, and highlights ongoing clinical trials and future clinical applications. EXPERT OPINION SG, LV, and T-DXd have demonstrated their potential to meaningfully improve clinical outcomes in patients with pretreated mTNBC, as demonstrated by notable response rates in phase I/II and, for SG, phase III clinical trials. Investigation of their use in combination with other agents, including PARP inhibitors and checkpoint inhibitors, is ongoing in the metastatic setting, and their application in early-stage TNBCs are under investigation. ADCs are therefore expected to redefine treatment paradigms in TNBC.
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Affiliation(s)
- Julia E McGuinness
- Department of Medicine, Division of Hematology and Oncology, Columbia University Irving Medical Center, New York, NY, USA
| | - Kevin Kalinsky
- Department of Medicine, Division of Hematology and Oncology, Emory University School of Medicine, Atlanta, GA, USA
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Chabot I, Zhao Q, Su Y. Systematic review of Real-World effectiveness of eribulin for locally advanced or metastatic breast cancer. Curr Med Res Opin 2020; 36:2025-2036. [PMID: 33044090 DOI: 10.1080/03007995.2020.1835853] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Eribulin mesylate (eribulin) is indicated for patients with metastatic breast cancer (MBC) who have previously received at least two chemotherapies in the US and for patients with locally advanced breast cancer (LABC) or MBC who have progressed after at least one chemotherapy in the European Union (EU). In both indications, prior therapy should include an anthracycline and a taxane in adjuvant or metastatic setting. Numerous studies evaluated eribulin in real-world (RW) breast cancer populations to reinforce its consistent effectiveness beyond registration randomized controlled trials (RCTs) that reported median overall survival (OS) of 13.1 and 15.9 months. In this systematic literature review (SLR), we summarize the cumulative evidence on eribulin's RW effectiveness in LABC/MBC. METHODS We searched through Medline/PubMed and Embase databases between 2012 and 2019 for articles reporting RW eribulin use in the second- or third-line or later LABC/MBC setting. Because eribulin showed greatest OS benefits in triple negative breast cancer (TNBC) in RCTs, we also reviewed this tumor subtype. OS and progression-free survival (PFS) were the effectiveness outcomes of interest. RESULTS Overall, 34 journal articles or abstracts met the selection criteria. Median OS ranged between 6.9 and 28.0 months; median PFS varied from 2.3 to 14.7 months. Eight studies reported OS outcomes for TNBC patients, and median OS ranged between 3.0 and 23.0 months. CONCLUSION The SLR showed high variability in OS and to a lesser extent in PFS associated with eribulin use in RW setting. Despite heterogeneity in line of use and patient subtypes, this SLR supports effectiveness of eribulin for LABC/MBC in clinical practice.
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Affiliation(s)
- Isabelle Chabot
- Faculty of Pharmacy, Montreal University, Montreal, Quebec, Canada
- Global Value & Access, Eisai Inc., Woodcliff Lake, NJ, USA
| | - Qi Zhao
- Global Value & Access, Eisai Inc., Woodcliff Lake, NJ, USA
| | - Yun Su
- Formerly of Global Value & Access, Eisai Inc., Woodcliff Lake, NJ, USA
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41
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Jhaveri KL, Dos Anjos CH, Taldone T, Wang R, Comen E, Fornier M, Bromberg JF, Ma W, Patil S, Rodina A, Pillarsetty N, Duggan S, Khoshi S, Kadija N, Chiosis G, Dunphy MP, Modi S. Measuring Tumor Epichaperome Expression Using [ 124I] PU-H71 Positron Emission Tomography as a Biomarker of Response for PU-H71 Plus Nab-Paclitaxel in HER2-Negative Metastatic Breast Cancer. JCO Precis Oncol 2020; 4:2000273. [PMID: 33283132 DOI: 10.1200/po.20.00273] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/09/2020] [Indexed: 12/13/2022] Open
Abstract
PURPOSE Epichaperome network maintenance is vital to survival of tumors that express it. PU-H71 is an epichaperome inhibitor that binds to the ATP-binding site of HSP90 and has demonstrated antitumor activity in breast cancer xenograft models and clinical safety in patients. PU-positron emission tomography (PET) is a theragnostic imaging tool that allows visualization of the epichaperome target. In this phase Ib trial, we present safety and tolerability for PU-H71 plus nab-paclitaxel in HER2-negative patients with metastatic breast cancer (MBC) and the utility of PU-PET as a noninvasive predictive biomarker. METHODS We performed a 3 + 3 dose-escalation study with escalating PU-H71 doses and standard nab-paclitaxel. The primary objective was to establish safety and determine maximum tolerated dose (MTD)/recommended phase 2 dose. Secondary objectives were to assess pharmacokinetics and clinical efficacy. Patients could enroll in a companion PU-PET protocol to measure epichaperome expression before treatment initiation to allow exploratory correlation with treatment benefit. RESULTS Of the 12 patients enrolled, dose-limiting toxicity occurred in one patient (G3 neutropenic fever) at dose level 1; MTD of PU-H71 was 300 mg/m2 plus nab-paclitaxel 260 mg/m2 administered every 3 weeks. Common toxicities included diarrhea, fatigue, peripheral neuropathy, and nausea. PU-H71 systemic exposure was not altered by nab-paclitaxel administration. Two of 12 patients had partial response (overall response rate, 17%) and the clinical benefit rate was 42% (5 of 12). Time to progression was associated with baseline epichaperome positivity and PU-H71 peak standard uptake value (SUV), with more durable disease control observed with high epichaperome levels. CONCLUSION The combination of PU-H71 and nab-paclitaxel was well tolerated, with evidence of clinical activity. More durable disease control without progression was observed in patients with high baseline epichaperome expression. A phase II trial of this combination with PU-PET as a companion diagnostic for patient selection is currently planned.
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Affiliation(s)
- Komal L Jhaveri
- Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Carlos H Dos Anjos
- Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Tony Taldone
- Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Rui Wang
- Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Elizabeth Comen
- Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Monica Fornier
- Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Jacqueline F Bromberg
- Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Weining Ma
- Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Sujata Patil
- Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Anna Rodina
- Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
| | | | | | - Sarhe Khoshi
- Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Nathan Kadija
- Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Gabriela Chiosis
- Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.,Program in Chemical Biology, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Mark P Dunphy
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Shanu Modi
- Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
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42
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Shi J, Liu F, Song Y. Progress: Targeted Therapy, Immunotherapy, and New Chemotherapy Strategies in Advanced Triple-Negative Breast Cancer. Cancer Manag Res 2020; 12:9375-9387. [PMID: 33061626 PMCID: PMC7533235 DOI: 10.2147/cmar.s272685] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2020] [Accepted: 09/11/2020] [Indexed: 12/11/2022] Open
Abstract
Triple-negative breast cancer (TNBC) is one of the most aggressive subtypes of breast cancer, accounting for approximately 15% of cases, and is defined by the lack of expression of hormone receptors (estrogen and progesterone receptors) and lack of amplification or overexpression of human epidermal growth receptor 2 (HER2). Due to the lack of targets of hormone receptors and HER2, treatment of TNBC or advanced TNBC relies on conventional chemotherapeutic agents, but their efficacy and prognosis are poor. In patients with advanced TNBC, poorer outcomes are observed. Recently, with the launch of clinical trials and advancements in molecular studies, targeted therapy for signaling transduction pathways, immunotherapy for immune checkpoints, and new chemotherapy strategies have provided feasible or potential therapeutic options for advanced TNBC. This review aimed to summarize recent progress in targeted therapy, immunotherapy, and chemotherapy for advanced TNBC.
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Affiliation(s)
- Jinhong Shi
- Cancer Center, The First Hospital of Jilin University, Changchun, Jilin, People’s Republic of China
| | - Feiqi Liu
- Cancer Center, The First Hospital of Jilin University, Changchun, Jilin, People’s Republic of China
| | - Yanqiu Song
- Cancer Center, The First Hospital of Jilin University, Changchun, Jilin, People’s Republic of China
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43
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Kazmi S, Chatterjee D, Raju D, Hauser R, Kaufman PA. Overall survival analysis in patients with metastatic breast cancer and liver or lung metastases treated with eribulin, gemcitabine, or capecitabine. Breast Cancer Res Treat 2020; 184:559-565. [PMID: 32808239 PMCID: PMC7599186 DOI: 10.1007/s10549-020-05867-0] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2020] [Accepted: 08/06/2020] [Indexed: 01/20/2023]
Abstract
Purpose The purpose of this study was to estimate the overall survival (OS) in real-world clinical practice in patients with metastatic breast cancer (MBC) and visceral metastases (liver or lung) treated in the third-line setting with eribulin, gemcitabine or capecitabine overall and in the major clinical categories of MBC (TNBC, HR+/HER2−, and HER2+). Methods A retrospective, observational study was conducted with de-identified patient electronic health records from the Cancer Treatment Centers of America (CTCA). Patients with a diagnosis of metastatic breast with lung or liver metastases, and treated with eribulin, gemcitabine, or capecitabine as third-line therapy were included in the analysis. Landmark survival was calculated as percentage of patients alive at 6, 12, 24, and 36 months. Overall survival was compared between treatment arms within TNBC and HR+/HER2− using log-rank analysis. Cox regression analyses was performed to estimate hazard ratios for comparison of treatments within TNBC and HR+/HER2− subtype. Results 443 patients with liver or lung metastases received third-line therapy with eribulin (n = 229), gemcitabine (n = 134), or capecitabine (n = 80). Eribulin patients had a higher percentage of patients alive at all landmark timepoints vs. gemcitabine, and a higher percentage of patients alive until 36 months vs. capecitabine. Median survival times showed that overall, and within the TNBC and HR+/HER2− subtype, patients receiving eribulin had a numerically higher median overall survival. Conclusions This real-world evidence study is consistent with randomized clinical trial data and demonstrates consistency of eribulin effectiveness in MBC patients with lung or liver metastases overall and in TNBC and HR+/HER2− disease.
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Affiliation(s)
- Shayma Kazmi
- Cancer Treatment Centers of America, Philadelphia, PA, USA.
| | - Debanjana Chatterjee
- US Health Economics Outcomes Research and Real World Evidence, Eisai Inc., Woodcliff Lake, NJ, USA
| | - Dheeraj Raju
- Cancer Treatment Centers of America Global, Inc., Boca Raton, FL, USA
| | - Rob Hauser
- Cancer Treatment Centers of America Global, Inc., Boca Raton, FL, USA
| | - Peter A Kaufman
- Larner College of Medicine, Division of Hematology/Oncology, University of Vermont Cancer Center, Burlington, VT, USA.
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44
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Ueno A, Maeda R, Kin T, Ito M, Kawasaki K, Ohtani S. Utility of the Absolute Lymphocyte Count and Neutrophil/Lymphocyte Ratio for Predicting Survival in Patients with Metastatic Breast Cancer on Eribulin: A Real-World Observational Study. Chemotherapy 2020; 64:259-269. [PMID: 32305977 DOI: 10.1159/000507043] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2020] [Accepted: 03/08/2020] [Indexed: 01/04/2023]
Abstract
INTRODUCTION Previous studies have suggested that the efficacy of eribulin is influenced by the activity of antitumor immunity of patients. Absolute lymphocyte count (ALC) and the neutrophil/lymphocyte ratio (NLR) are easily available parameters associated with the immunological status of patients. OBJECTIVE Here we tried to classify patients' immunological status by using the scatter plot of ALC and NLR, and investigated its utility for predicting survival among patients with metastatic breast cancer receiving eribulin. METHODS The medical records of 125 patients who received eribulin for metastatic breast cancer at our hospital between July 2011 and April 2019 were retrospectively reviewed. Uni- and multivariate analyses were performed to determine the association between baseline ALC/NLR and progression-free survival (PFS)/overall survival (OS). The cutoff values for ALC and NLR were determined using scatter plot analysis. RESULTS The entire cohort was classified into immunologically favorable (ALC ≥1,500/µL, 30 patients), intermediate (ALC <1,500/µL, NLR <5.0, 76 patients), and unfavorable (NLR ≥5.0, 19 patients) groups. Univariate analysis showed significant differences in PFS and OS between the groups, whereas multivariate analysis revealed that ALC ≥1,500/µL and NLR ≥5.0 were independent predictors of PFS, with adjusted hazard ratios (95% CI) of 0.57 (0.33-0.99) and 1.78 (1.00-3.15), respectively. NLR ≥5.0 was also associated with worse OS (adjusted hazard ratio: 0.55; 95% CI 0.35-0.88; p = 0.013). CONCLUSIONS Among patients with metastatic breast cancer receiving eribulin, survival outcomes were well stratified according to baseline peripheral blood ALC and NLR. Accordingly, high ALC and NLR can be used as predictive markers for longer disease control and worse survival, respectively.
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Affiliation(s)
- Ayako Ueno
- Division of Breast Surgery, Hiroshima City Hiroshima Citizens Hospital, Hiroshima, Japan,
| | - Reina Maeda
- Division of Breast Surgery, Hiroshima City Hiroshima Citizens Hospital, Hiroshima, Japan
| | - Takanori Kin
- Division of Breast Surgery, Hiroshima City Hiroshima Citizens Hospital, Hiroshima, Japan
| | - Mitsuya Ito
- Division of Breast Surgery, Hiroshima City Hiroshima Citizens Hospital, Hiroshima, Japan
| | - Kensuke Kawasaki
- Division of Breast Surgery, Hiroshima City Hiroshima Citizens Hospital, Hiroshima, Japan
| | - Shoichiro Ohtani
- Division of Breast Surgery, Hiroshima City Hiroshima Citizens Hospital, Hiroshima, Japan
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53BP1 Accumulation in Circulating Tumor Cells Identifies Chemotherapy-Responsive Metastatic Breast Cancer Patients. Cancers (Basel) 2020; 12:cancers12040930. [PMID: 32283863 PMCID: PMC7226269 DOI: 10.3390/cancers12040930] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2020] [Revised: 04/03/2020] [Accepted: 04/07/2020] [Indexed: 12/17/2022] Open
Abstract
Evidence suggests that the DNA end-binding protein p53-binding protein 1 (53BP1) is down-regulated in subsets of breast cancer. Circulating tumor cells (CTCs) provide accessible “biopsy material” to track cell traits and functions and their alterations during treatment. Here, we prospectively monitored the 53BP1 status in CTCs from 67 metastatic breast cancer (MBC) patients with HER2- CTCs and known hormone receptor (HR) status of the primary tumor and/or metastases before, during, and at the end of chemotherapeutic treatment with Eribulin. Nuclear 53BP1 staining and genomic integrity were evaluated by immunocytochemical and whole-genome-amplification-based polymerase chain reaction (PCR) analysis, respectively. Comparative analysis of CTCs from patients with triple-negative and HR+ tumors revealed elevated 53BP1 levels in CTCs from patients with HR+ metastases, particularly following chemotherapeutic treatment. Differences in nuclear 53BP1 signals did not correlate with genomic integrity in CTCs at baseline or with nuclear γH2AX signals in MBC cell lines, indicating that 53BP1 detected features beyond DNA damage. Kaplan–Meier analysis revealed an increasing association between nuclear 53BP1-positivity and progression-free survival (PFS) during chemotherapy until the final visit. Our data suggest that 53BP1 detection in CTCs could be a useful marker to capture dynamic changes of chemotherapeutic responsiveness in triple-negative and HR+ MBC.
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Shingaki S, Kogawa T, Shimokawa M, Harano K, Naito Y, Kusuhara S, Fujimoto Y, Matsubara N, Hosono A, Mukai H, Onishi T, Hojo T, Mukohara T. Use of eribulin as an earlier-line chemotherapy for patients with HER2-negative metastatic breast cancer. J Cancer 2020; 11:4099-4105. [PMID: 32368292 PMCID: PMC7196254 DOI: 10.7150/jca.37670] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2019] [Accepted: 03/27/2020] [Indexed: 11/05/2022] Open
Abstract
Background: Previous prospective studies have shown that eribulin improves the survival in patients with metastatic breast cancer (MBC). However, the optimal timing of its administration to achieve the longest extended survival and the efficacy of using eribulin monotherapy as earlier-line chemotherapy are yet unclear. Methods: We identified all consecutive female patients with MBC who received any chemotherapeutic intervention for metastatic disease at our institution between July 2012 and December 2017, excluding patients with HER2-positive disease. Those who received eribulin monotherapy for MBC were classified under the eribulin cohort, whereas those who never received eribulin were included in the non-eribulin (Non-E) cohort. Among the patients in the eribulin cohort, those who received eribulin as the first- or second-line chemotherapy for MBC were further classified under the earlier-line eribulin (EE), and otherwise classified under the later-line eribulin (LE) cohorts. The survival of patients was assessed using the log-rank test. A multivariable Cox proportional hazards model was used to assess the independent efficacy and timing of eribulin monotherapy. The inverse probability of treatment weighting (IPTW) estimate was utilized to compare the EE and LE cohorts. Results: Of the 507 patients who were initially screened, 226 were included after an intensive chart review: 93, 49, and 84 patients were included in the Non-E, EE, and LE cohorts, respectively. The eribulin cohort showed significantly longer overall survival than the Non-E cohort (30.3 vs. 22.2 months, p = 0.0217). No significant difference was observed in the progression-free survival of the EE and LE cohorts (3.4 vs. 4.4 months, p = 0.1337) after adjusting for clinically relevant factors using IPTW estimates. LE cohort showed good overall survival (OS) compared with patient group of Non-E and EE by log-rank testing (p = 0.0398), although multivariate analysis did not demonstrate eribulin administration timing as an independent prognostic factor of OS. OS was defined from the initiation of first-line chemotherapy date. Conclusions: Our data provided additional insights regarding the use of eribulin monotherapy as earlier-line chemotherapy. However, the optimal timing of eribulin monotherapy for MBC was not determined in the current study.
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Affiliation(s)
- Sumito Shingaki
- Departments of Breast and Medical Oncology, National Cancer Center Hospital East, Kashiwa, Japan.,Department of Developmental Therapeutics, National Cancer Center Hospital East, Kashiwa, Japan
| | - Takahiro Kogawa
- Departments of Breast and Medical Oncology, National Cancer Center Hospital East, Kashiwa, Japan.,Department of Developmental Therapeutics, National Cancer Center Hospital East, Kashiwa, Japan
| | - Mototsugu Shimokawa
- Cancer Biostatistics Laboratory, Clinical Research Institute, National Kyushu Cancer Center, Fukuoka, Japan.,Department of Biostatistics, Yamaguchi University Graduate School of Medicine, Ube, Japan
| | - Kenichi Harano
- Departments of Breast and Medical Oncology, National Cancer Center Hospital East, Kashiwa, Japan.,Department of Developmental Therapeutics, National Cancer Center Hospital East, Kashiwa, Japan
| | - Yoichi Naito
- Departments of Breast and Medical Oncology, National Cancer Center Hospital East, Kashiwa, Japan.,Department of Developmental Therapeutics, National Cancer Center Hospital East, Kashiwa, Japan
| | - Shota Kusuhara
- Departments of Breast and Medical Oncology, National Cancer Center Hospital East, Kashiwa, Japan
| | - Yumi Fujimoto
- Departments of Breast and Medical Oncology, National Cancer Center Hospital East, Kashiwa, Japan
| | - Nobuaki Matsubara
- Departments of Breast and Medical Oncology, National Cancer Center Hospital East, Kashiwa, Japan
| | - Ako Hosono
- Departments of Breast and Medical Oncology, National Cancer Center Hospital East, Kashiwa, Japan
| | - Hirofumi Mukai
- Departments of Breast and Medical Oncology, National Cancer Center Hospital East, Kashiwa, Japan
| | - Tatsuya Onishi
- Department of Breast Surgery, National Cancer Center Hospital East, Kashiwa, Japan
| | - Takashi Hojo
- Department of Breast Surgery, National Cancer Center Hospital East, Kashiwa, Japan
| | - Toru Mukohara
- Departments of Breast and Medical Oncology, National Cancer Center Hospital East, Kashiwa, Japan
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N-Cadherin mRNA Levels in Peripheral Blood Could Be a Potential Indicator of New Metastases in Breast Cancer: A Pilot Study. Int J Mol Sci 2020; 21:ijms21020511. [PMID: 31947504 PMCID: PMC7013704 DOI: 10.3390/ijms21020511] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2020] [Revised: 01/12/2020] [Accepted: 01/12/2020] [Indexed: 01/29/2023] Open
Abstract
Background: There is growing evidence that patients with metastatic breast cancer whose disease progresses from a new metastasis (NM) have a worse prognosis than that of patients whose disease progresses from a pre-existing metastasis. The aim of this pilot study is to identify a blood biomarker predicting NM in breast cancer. Methods: The expression of epithelial (cytokeratin 18/19) or mesenchymal (plastin-3, vimentin, and N-cadherin) markers in the peripheral blood (PB) of recurrent breast cancer patients undergoing chemotherapy with eribulin or S-1 was measured over the course of treatment by RT-qPCR. The clinical significance of preoperative N-cadherin expression in the PB or tumor tissues of breast cancer patients undergoing curative surgery was assessed by RT-qPCR or using public datasets. Finally, N-cadherin expression in specific PB cell types was assessed by RT-qPCR. Results: The expression levels of the mesenchymal markers N-cadherin and vimentin were high in the NM cases, whereas that of the epithelial marker cytokeratin 18 was high in the pre-existing metastasis cases. High preoperative N-cadherin expression in PB or tumor tissues was significantly associated with poor recurrence-free survival. N-cadherin was expressed mainly in polymorphonuclear leukocytes in PB. Conclusion: N-cadherin mRNA levels in blood may serve as a novel prognostic biomarker predicting NM, including recurrence, in breast cancer patients.
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48
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Li CH, Karantza V, Aktan G, Lala M. Current treatment landscape for patients with locally recurrent inoperable or metastatic triple-negative breast cancer: a systematic literature review. Breast Cancer Res 2019; 21:143. [PMID: 31842957 PMCID: PMC6916124 DOI: 10.1186/s13058-019-1210-4] [Citation(s) in RCA: 94] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2019] [Accepted: 10/15/2019] [Indexed: 12/19/2022] Open
Abstract
Background Metastatic triple-negative breast cancer (mTNBC), an aggressive histological subtype, has poor prognosis. Chemotherapy remains standard of care for mTNBC, although no agent has been specifically approved for this breast cancer subtype. Instead, chemotherapies approved for metastatic breast cancer (MBC) are used for mTNBC (National Comprehensive Cancer Network Guidelines [NCCN] v1.2019). Atezolizumab in combination with nab-paclitaxel was recently approved for programmed death-ligand 1 (PD-L1)–positive locally advanced or metastatic TNBC. Published historical data were reviewed to characterize the efficacy of NCCN-recommended (v1.2016) agents as first-line (1L) and second-line or later (2L+) treatment for patients with locally recurrent inoperable or metastatic TNBC (collectively termed mTNBC herein). Methods A systematic literature review was performed, examining clinical efficacy of therapies for mTNBC based on NCCN v1.2016 guideline recommendations. Data from 13 studies, either published retrospective mTNBC subgroup analyses based on phase III trials in MBC or phase II trials in mTNBC, were included. Results A meta-analysis of mTNBC subgroups from three phase III trials in 1L MBC reported pooled objective response rate (ORR) of 23%, median overall survival (OS) of 17.5 months, and median progression-free survival (PFS) of 5.4 months with single-agent chemotherapy. In two subgroup analyses from a phase III study and a phase II trial (n = 40 each), median duration of response (DOR) to 1L chemotherapy for mTNBC was 4.4–6.6 months; therefore, responses were not durable. A meta-analysis of seven cohorts showed the pooled ORR for 2L+ chemotherapy was 11% (95% CI, 9–14%). Median DOR to 2L+ chemotherapy in mTNBC was also limited (4.2–5.9 months) per two subgroup analyses from a phase III study. No combination chemotherapy regimens recommended by NCCN v1.2016 for treatment of MBC showed superior OS to single agents. Conclusions Chemotherapies have limited effectiveness and are associated with unfavorable toxicity profiles, highlighting a considerable unmet medical need for improved therapeutic options in mTNBC. In addition to the recently approved combination of atezolizumab and nab-paclitaxel for PD-L1–positive mTNBC, new treatments resulting in durable clinical responses, prolonged survival, and manageable safety profile would greatly benefit patients with mTNBC.
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49
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Cortes J, Twelves C. Impact of the number of prior chemotherapy regimens on outcomes for patients with metastatic breast cancer treated with eribulin: A post hoc pooled analysis. Breast J 2019; 26:1347-1351. [PMID: 31782589 PMCID: PMC7496313 DOI: 10.1111/tbj.13686] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2019] [Accepted: 10/18/2019] [Indexed: 12/20/2022]
Abstract
In a pivotal phase 3 study (Study 305), eribulin mesylate improved overall survival (OS) in patients with previously treated metastatic breast cancer (MBC) compared with treatment of physician's choice (TPC). This post hoc, pooled subgroup analysis of two phase 3 studies (Study 305 and Study 301) reports the influence of the number of prior chemotherapy regimens (0‐6) on OS in patients with locally advanced/MBC randomized to eribulin versus TPC/capecitabine. Patients with ≤ 3 prior chemotherapies for locally advanced/MBC had longer median OS with eribulin (15.3 months) versus control (13.2 months; hazard ratio, 0.858; P = .01).
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Affiliation(s)
- Javier Cortes
- IOB Institute of Oncology, Quironsalud Group, Madrid & Barcelona, Spain.,Vall d´Hebron Institute of Oncology, Barcelona, Spain
| | - Chris Twelves
- Leeds Institute of Medical Research at St James's, University of Leeds and Leeds Teaching Hospitals Trust, Leeds, UK
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50
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Pizzuti L, Krasniqi E, Barchiesi G, Mazzotta M, Barba M, Amodio A, Massimiani G, Pelle F, Kayal R, Vizza E, Grassadonia A, Tomao S, Venuti A, Gamucci T, Marchetti P, Natoli C, Sanguineti G, Ciliberto G, Vici P. Eribulin in Triple Negative Metastatic Breast Cancer: Critic Interpretation of Current Evidence and Projection for Future Scenarios. J Cancer 2019; 10:5903-5914. [PMID: 31762800 PMCID: PMC6856581 DOI: 10.7150/jca.35109] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2019] [Accepted: 07/18/2019] [Indexed: 12/14/2022] Open
Abstract
Triple negative breast cancer (TNBC) is characterized by distinctive biological features that confer an aggressive clinical behavior. In TNBC patients, the absence of well-defined driver pathways such as hormonal receptor expression or hyperactivation of the human epidermal growth factor receptor 2 (HER2) significantly reduce the spectrum of therapeutic options, which are currently mainly confined to chemotherapy. Thus far, median overall survival for patients with metastatic TNBC is about 9-12 months with conventional cytotoxic agents. However, the heterogeneity recently revealed at a gene expression level inside the TNBC family may help inform therapeutic decisions concerning the use of chemotherapy and hopefully lead the way to novel targeted options that include immunotherapy. Eribulin, a halichondrin class antineoplastic drug, is currently recommended for treatment of HER2 negative metastatic or recurrent breast cancer (BC) previously exposed to anthracyclines and taxanes, also for patients with a TNBC. It is currently indicated from the second line of treatment. In this review, we aim to analyze a wide range of cumulated evidence on eribulin use in TNBC including preclinical studies, intervention and observational clinical trials. Data from the real-world setting and the emerging evidence increasingly substantiating the rationale for combinations with new generation treatment strategies, e.g., PARP-inhibitors, immune checkpoint inhibitors, will be also discussed.
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Affiliation(s)
- Laura Pizzuti
- Division of Medical Oncology 2, IRCCS Regina Elena National Cancer Institute, Via Elio Chianesi, 53, 00144 Rome, Italy
| | - Eriseld Krasniqi
- Division of Medical Oncology 2, IRCCS Regina Elena National Cancer Institute, Via Elio Chianesi, 53, 00144 Rome, Italy
| | - Giacomo Barchiesi
- Division of Medical Oncology 2, IRCCS Regina Elena National Cancer Institute, Via Elio Chianesi, 53, 00144 Rome, Italy
| | - Marco Mazzotta
- Department of Clinical and Molecular Medicine, "Sapienza" University of Rome, Azienda Ospedaliera Sant'Andrea, 00189 Rome, Italy
| | - Maddalena Barba
- Division of Medical Oncology 2, IRCCS Regina Elena National Cancer Institute, Via Elio Chianesi, 53, 00144 Rome, Italy
| | - Antonella Amodio
- Division of Medical Oncology 2, IRCCS Regina Elena National Cancer Institute, Via Elio Chianesi, 53, 00144 Rome, Italy
| | - Gioia Massimiani
- Division of Medical Oncology 2, IRCCS Regina Elena National Cancer Institute, Via Elio Chianesi, 53, 00144 Rome, Italy
| | - Fabio Pelle
- Department of Surgery, IRCCS Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144, Rome, Italy
| | - Ramy Kayal
- Radiology and Diagnostic Imaging Department, IRCCS Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144, Rome, Italy
| | - Enrico Vizza
- Department of Experimental Clinical Oncology, Gynecologic Oncology Unit, IRCCS "Regina Elena" National Cancer Institute, Rome, Italy
| | - Antonino Grassadonia
- Department of Medical, Oral & Biotechnological Sciences University G. D'Annunzio, Chieti-Pescara, Italy
| | - Silverio Tomao
- Department of Radiological, Oncological and Anatomo-Pathological Sciences, 'Sapienza' University of Rome, Policlinico Umberto I, I-00161 Rome, Italy
| | - Aldo Venuti
- HPV-Unit-UOSD Tumor Immunology and Immunotherapy, IRCCS Regina Elena National Cancer Institute, Via Elio Chianesi 53, Rome, Italy
| | | | - Paolo Marchetti
- Department of Clinical and Molecular Medicine, "Sapienza" University of Rome, Azienda Ospedaliera Sant'Andrea, 00189 Rome, Italy
| | - Clara Natoli
- Department of Medical, Oral & Biotechnological Sciences University G. D'Annunzio, Chieti-Pescara, Italy
| | - Giuseppe Sanguineti
- Department of Radiation Oncology, IRCCS Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144, Rome, Italy
| | - Gennaro Ciliberto
- Scientific Direction , IRCCS Regina Elena National Cancer Institute , Via Elio Chianesi 53, 00144, Rome, Italy
| | - Patrizia Vici
- Division of Medical Oncology 2, IRCCS Regina Elena National Cancer Institute, Via Elio Chianesi, 53, 00144 Rome, Italy
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