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Bonfill Cosp X, Savall-Esteve O, Bracchiglione J, Requeijo C, Santero M. Mismatch between evidence and related clinical recommendations about the treatment of advanced esophageal cancer patients with anticancer drugs: A critical historical review. J Cancer Policy 2025; 44:100580. [PMID: 40147630 DOI: 10.1016/j.jcpo.2025.100580] [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: 07/04/2024] [Revised: 02/19/2025] [Accepted: 03/21/2025] [Indexed: 03/29/2025]
Abstract
PURPOSE to analyze the most robust research and recommendations that have informed the potential superiority of treatments with anticancer drugs over any type of supportive care for advanced esophageal cancer (EC). METHODS We conducted a critical historical review. First, we identified randomized clinical trials (RCTs) from a previous scoping review conducted by our research group, ASTAC, updating the search strategy. Second, we searched for the most important and recognized international clinical practice guidelines (CPGs) in advanced EC. Finally, we performed a systematic document analysis to compare whether the recommendations proposed in the CPGs were supported by the previously identified relevant evidence. RESULTS We identified and assessed 15 RCTs and 11 CPGs from ESMO (eight), ASCO (two), and NICE (one) published over the last 40 years. There is a clear mismatch between these guidelines' recommendations and the available RCTs regarding the efficacy of anticancer drugs compared to best supportive care (BSC). CONCLUSION There is a lack of consistent evidence to support the treatment of advanced EC patients with anticancer drugs, and a notable mismatch exists between the available evidence and the recommendations made by relevant CPGs. As a result, these guidelines may be biased in favoring the use of anticancer drugs over supportive care and in consequence it is advisable to be very prudent when proposing systemic treatments to patients with advanced EC. Further rigorous and independent research is needed to better evaluate the true benefits of anticancer treatments in advanced EC and to update the CPGs accordingly.
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Affiliation(s)
- Xavier Bonfill Cosp
- Iberoamerican Cochrane Centre, Barcelona, Spain; Universitat Autònoma Barcelona (UAB), Barcelona, Spain; CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain; Institut de Recerca Sant Pau (IR Sant Pau), Barcelona, Spain
| | - Olga Savall-Esteve
- Iberoamerican Cochrane Centre, Barcelona, Spain; Institut de Recerca Sant Pau (IR Sant Pau), Barcelona, Spain
| | - Javier Bracchiglione
- Iberoamerican Cochrane Centre, Barcelona, Spain; Universitat Autònoma Barcelona (UAB), Barcelona, Spain; Interdisciplinary Centre for Health Studies (CIESAL), Universidad de Valparaíso, Viña del Mar, Chile; CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain; Institut de Recerca Sant Pau (IR Sant Pau), Barcelona, Spain
| | - Carolina Requeijo
- Iberoamerican Cochrane Centre, Barcelona, Spain; Institut de Recerca Sant Pau (IR Sant Pau), Barcelona, Spain
| | - Marilina Santero
- Iberoamerican Cochrane Centre, Barcelona, Spain; Universitat Autònoma Barcelona (UAB), Barcelona, Spain; Institut de Recerca Sant Pau (IR Sant Pau), Barcelona, Spain.
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Liu Y, Wang Y, Zhu Y, Wu T, Liu Z, Zhou J, Yuan Y, Yang M, Liu B, Tan Z, Zhuang W, Chen J, Li N, Wang Y, Hu X, Wang L, Yu H, Wang Q, Zhu J, Huang J. HLX07 alone or combined with serplulimab, cisplatin and 5-fluorouracil for advanced esophageal squamous cell carcinoma: A phase 2 study. Cancer Commun (Lond) 2024; 44:1431-1443. [PMID: 39446605 DOI: 10.1002/cac2.12621] [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: 03/15/2024] [Revised: 10/11/2024] [Accepted: 10/13/2024] [Indexed: 10/26/2024] Open
Abstract
BACKGROUND The combination of anti-PD-1 antibody serplulimab and chemotherapy is considered standard first-line therapy for advanced esophageal squamous cell carcinoma (ESCC), but few later-line treatments are available. Here we evaluated the therapeutic efficacy of the recombinant, humanized anti-EGFR antibody HLX07 when used alone or together with serplulimab and chemotherapy against advanced ESCC. METHODS This open-label, non-randomized, two-cohort, phase 2 trial involved patients 18-75 years old with histologically or cytologically confirmed locally advanced, unresectable, or metastatic ESCC, and an Eastern Cooperative Oncology Group performance status of 0-1. Patients who had failed first-line immuno-chemotherapy or at least two lines of other systemic therapy received HLX07 monotherapy intravenously at a dose of 1,000 mg once every 2 weeks (Q2W). Patients with no prior systemic therapy received HLX07 (1,000 mg, day 1) and serplulimab (200 mg, day 1) intravenously Q2W for up to 2 years, concurrently with cisplatin (50 mg/m2, day 1) for up to 8 cycles and 5-fluorouracil (1,200 mg/m2, days 1-2) for up to 12 cycles intravenously Q2W. The primary endpoints were progression-free survival (PFS) and objective response rate (ORR). RESULTS Overall, 50 patients were enrolled. In the HLX07 monotherapy group, ORR was 15.0% (3/20), and the median PFS was 1.5 months (95% confidence interval [CI], 1.3 to 3.7). The median duration of response was not reached, and the rate of patients showing an objective response lasting at least 6 months was 66.7% (95% CI, 5.4 to 94.5). Two (10.0%, 2/20) patients experienced grade 3-4 treatment-related adverse events (TRAEs), including hypomagnesemia, hypocalcemia, and fatigue. No patient experienced grade 5 TRAEs. In the HLX07 combination group, the ORR was 60.0% (18/30), and the median PFS was 7.8 months (95% CI, 3.3 to 9.1). Fourteen (46.7%, 14/30) patients experienced grade 3-4 TRAEs, and one (3.3%, 1/30) patient died due to serplulimab-related pneumonitis. CONCLUSIONS HLX07 monotherapy and its combination with serplulimab and chemotherapy showed manageable toxicity and promising antitumor activity in patients with recurrent or metastatic ESCC. Randomized controlled trials are warranted to further establish the safety and efficacy of HLX07 against ESCC. TRIAL REGISTRATION This trial was registered at Clinicaltrials.gov (NCT05221658).
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Affiliation(s)
- Yun Liu
- 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, P. R. China
| | - Yanfeng Wang
- Department of Comprehensive Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China
| | - Yanrong Zhu
- 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, P. R. China
| | - Tao Wu
- Department of Internal Medicine, Anyang Tumor Hospital, Anyang, Henan, P. R. China
| | - Zhenyang Liu
- Department of Gastroenterology and Urology, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, P. R. China
| | - Jin Zhou
- Department of Medical Oncology, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Cancer Hospital Affiliated to the School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, P. R. China
| | - Yuan Yuan
- Department of Medical Oncology, Xuzhou Central Hospital, Xuzhou, Jiangsu, P. R. China
| | - Mudan Yang
- Department of Gastroenterology, Shanxi Cancer Hospital, Taiyuan, Shanxi, P. R. China
| | - Bo Liu
- Department of Medical Oncology, Shandong Cancer Hospital & Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, P. R. China
| | - Zhenbo Tan
- Department of Thoracic Surgery, Xingtai People's Hospital, Xingtai, Hebei, P. R. China
| | - Wu Zhuang
- Department of Medical Oncology, Fujian Cancer Hospital, Fuzhou, Fujian, P. R. China
| | - Jiayan Chen
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, P. R. China
| | - Ning Li
- Department of Medical Oncology, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, Henan, P. R. China
| | - Ying Wang
- Department of Medical Oncology, Cancer Hospital Chinese Academy of Medical Sciences, Shenzhen Center, Shenzhen, Guangdong, P. R. China
| | - Xuhui Hu
- Global Product Development, Shanghai Henlius Biotech Inc., Shanghai, P. R. China
| | - Lin Wang
- Global Product Development, Shanghai Henlius Biotech Inc., Shanghai, P. R. China
| | - Haoyu Yu
- Global Product Development, Shanghai Henlius Biotech Inc., Shanghai, P. R. China
| | - Qingyu Wang
- Global Product Development, Shanghai Henlius Biotech Inc., Shanghai, P. R. China
| | - Jun Zhu
- Global Product Development, Shanghai Henlius Biotech Inc., Shanghai, P. R. China
| | - Jing Huang
- 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, P. R. China
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Jubashi A, Kotani D, Kojima T, Takebe N, Shitara K. Current landscape of targeted therapy in esophageal squamous cell carcinoma. Curr Probl Cancer 2024; 53:101152. [PMID: 39454516 DOI: 10.1016/j.currproblcancer.2024.101152] [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: 05/09/2024] [Revised: 09/30/2024] [Accepted: 10/03/2024] [Indexed: 10/28/2024]
Abstract
Esophageal cancer is the seventh most common malignancy worldwide and is primarily categorized into adenocarcinoma and squamous cell carcinoma (SCC), with the predominant histological type varying by region. In Western countries, including the United States, adenocarcinoma is more prevalent, whereas in East Asian countries, SCC is more common, with it constituting 86% of cases in Japan. Although there has been an increasing trend of adenocarcinoma in Western populations, SCC still accounts for the majority of esophageal cancer cases globally. Cytotoxic chemotherapy has been the mainstay of treatment, however, targeted therapies including EGFR, FGFR, PI3K, or CDK4/6, despite showing preliminary efficacy signals, have not yet received regulatory approval. Recently, immune checkpoint inhibitors (ICIs) have shown therapeutic efficacy and have been approved as a monotherapy or combination therapy for advanced esophageal SCC (ESCC). Although PD-L1 expression is the only clinically applicable biomarker for first-line therapy with ICIs in ESCC, responses to ICIs are various, and novel predictive biomarkers are under investigation. Furthermore, novel antibody-drug conjugates (ADC) hold promise for advanced ESCC. This review includes the current landscape and future perspectives of potential targeted therapy for advanced ESCC.
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Affiliation(s)
- Amane Jubashi
- Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan
| | - Daisuke Kotani
- Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
| | - Takashi Kojima
- Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan
| | - Naoko Takebe
- Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, National Institutes of Health, MD, USA
| | - Kohei Shitara
- Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan
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Shi H, Tan Y, Ma C, Wei Y, Shi F, Wang J, Xu C, Liang R. Efficacy and safety evaluation of first-line systemic treatments for unresectable esophageal squamous cell carcinoma: a network meta-analysis. Front Oncol 2024; 14:1397960. [PMID: 39314629 PMCID: PMC11416913 DOI: 10.3389/fonc.2024.1397960] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2024] [Accepted: 08/16/2024] [Indexed: 09/25/2024] Open
Abstract
Objective To evaluate the efficacy and safety of various first-line initial treatment systemic regimens for patients with unresectable esophageal squamous carcinoma(ESCC), utilizing a network meta-analysis approach. Methods A comprehensive search for randomized controlled trials focusing on the primary treatment of esophageal cancer ESCC was conducted across multiple databases including PubMed, Embase, Cochrane Library, and Web of Science, up until November 17, 2023. The quality of the included studies was rigorously assessed using Review Manager software. Subsequently, data analysis was meticulously carried out employing R software. The first-line treatment regimens examined were: CD (Cisplatin + Docetaxel), CET-CF (Cetuximab + Cisplatin + Fluorouracil), CF (Cisplatin + Fluorouracil), N-CF (Nivolumab + Cisplatin + Fluorouracil), NI (Nivolumab + Ipilimumab), Nim-CF (Nimotuzumab + Cisplatin + Fluorouracil), P-CF (Pembrolizumab + Cisplatin + Fluorouracil), and Ser-CF (Serplulimab + Cisplatin + Fluorouracil). The Primary endpoints included the overall survival(OS),progression-free survival (PFS),objective response rate (ORR) and disease control rate (DCR).The secondary endpoint was adverse effects(AEs). Results The analysis encompassed eight studies, incorporating a total of 3,051 patients with untreated esophageal cancer. There are 45 people in the CD regimen,32 in the CET-CF regimen,1,212 in the CF regimen,447 in the N-CF regimen,456 in the NI regimen,53 in the Nim-CF regimen,447 in the P-CF regimen and 368 in the Ser-CF regimen. The network meta-analysis revealed that, in comparison to the CF regimen, the other regimens (CD, CET-CF, N-CF, NI, Nim-CF, P-CF, and Ser-CF) did not demonstrate a statistically significant impact on overall survival (OS) or progression-free survival (PFS). However, Ser-CF potentially offers superior outcomes in terms of OS and PFS when juxtaposed with other regimens. Notably, N-CF was associated with a substantial increase in the objective response rate (ORR), and CET-CF markedly improved the disease control rate (DCR). In terms of adverse effects, N-CF was more likely to cause anorexia, whereas CET-CF was significantly associated with nausea, vomiting, neutropenia, and skin disorders. Conclusion The current evidence suggests that N-CF may provide the most favorable outcomes in terms of ORR, while CET-CF could be the optimal choice for enhancing DCR in patients with untreated esophageal cancer.
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Affiliation(s)
- Huiling Shi
- Department of Oncology, The Fourth Affiliated Hospital of Soochow University, Suzhou, China
- Division of Clinical Oncology, Medical Center of Soochow University, Suzhou, China
| | - Yong Tan
- School of Physical Education, Soochow University, Suzhou, China
| | - Chao Ma
- Department of Oncology, The Fourth Affiliated Hospital of Soochow University, Suzhou, China
- Division of Clinical Oncology, Medical Center of Soochow University, Suzhou, China
| | - Yushan Wei
- Department of Oncology, The Fourth Affiliated Hospital of Soochow University, Suzhou, China
- Division of Clinical Oncology, Medical Center of Soochow University, Suzhou, China
| | - Fengling Shi
- Department of Oncology, The Fourth Affiliated Hospital of Soochow University, Suzhou, China
- Division of Clinical Oncology, Medical Center of Soochow University, Suzhou, China
| | - Juan Wang
- Department of Oncology, The Fourth Affiliated Hospital of Soochow University, Suzhou, China
- Division of Clinical Oncology, Medical Center of Soochow University, Suzhou, China
| | - Caihua Xu
- Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Rongrui Liang
- Department of Oncology, The Fourth Affiliated Hospital of Soochow University, Suzhou, China
- Division of Clinical Oncology, Medical Center of Soochow University, Suzhou, China
- Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, China
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Mitamura A, Tsujinaka S, Nakano T, Sawada K, Shibata C. Treatment Strategies for Locoregional Recurrence in Esophageal Squamous-Cell Carcinoma: An Updated Review. Cancers (Basel) 2024; 16:2539. [PMID: 39061179 PMCID: PMC11274925 DOI: 10.3390/cancers16142539] [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: 06/07/2024] [Revised: 07/02/2024] [Accepted: 07/12/2024] [Indexed: 07/28/2024] Open
Abstract
Emerging evidence has shown remarkable advances in the multimodal treatment of esophageal squamous-cell carcinoma. Despite these advances, the oncological outcomes for advanced esophageal cancer remain controversial due to the frequent observation of local recurrence in the regional or other lymph nodes and distant metastasis after curative treatment. For cases of locoregional recurrence in the cervical lymph nodes alone, salvage surgery with lymph node dissection generally provides a good prognosis. However, if recurrence occurs in multiple regions, the oncological efficacy of surgery may be limited. Radiotherapy/chemoradiotherapy can be employed for unresectable or recurrent cases, as well as for selected cases in neo- or adjuvant settings. Dose escalation and toxicity are potential issues with conventional three-dimensional conformal radiotherapy; however, more precise therapeutic efficacy can be obtained using technical modifications with improved targeting and conformality, or with the use of proton beam therapy. The introduction of immune checkpoint inhibitors, including pembrolizumab or nivolumab, in addition to chemotherapy, has been shown to improve the overall survival in unresectable, advanced/recurrent cases. For patients with lymph node recurrence in multiple regions, chemotherapy (5-fluorouracil [5-FU] plus cisplatin) and combination therapy with nivolumab and ipilimumab have shown comparable oncological efficacy. Further prospective studies are needed to improve the treatment outcomes in patients with esophageal cancer with locoregional recurrence.
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Affiliation(s)
| | - Shingo Tsujinaka
- Division of Gastroenterological Surgery, Department of Surgery, Tohoku Medical and Pharmaceutical University, Sendai 983-8536, Japan
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Feng Z, Luan M, Zhu W, Xing Y, Ma X, Wang Y, Jia Y. Targeted ferritinophagy in gastrointestinal cancer: from molecular mechanisms to implications. Arch Toxicol 2024; 98:2007-2018. [PMID: 38602537 DOI: 10.1007/s00204-024-03745-y] [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: 02/27/2024] [Accepted: 03/20/2024] [Indexed: 04/12/2024]
Abstract
Gastrointestinal cancer is a significant global health burden, necessitating the development of novel therapeutic strategies. Emerging evidence has highlighted the potential of targeting ferritinophagy as a promising approach for the treatment of gastrointestinal cancer. Ferritinophagy is a form of selective autophagy that is mediated by the nuclear receptor coactivator 4 (NCOA4). This process plays a crucial role in regulating cellular iron homeostasis and has been implicated in various pathological conditions, including cancer. This review discusses the molecular mechanisms underlying ferritinophagy and its relevance to gastrointestinal cancer. Furthermore, we highlight the potential therapeutic implications of targeting ferritinophagy in gastrointestinal cancer. Several approaches have been proposed to modulate ferritinophagy, including small molecule inhibitors and immunotherapeutic strategies. We discuss the advantages and challenges associated with these therapeutic interventions and provide insights into their potential clinical applications.
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Affiliation(s)
- Zhaotian Feng
- Department of Medical Laboratory, Shandong Second Medical University, Weifang, 261053, People's Republic of China
- Research Center of Basic Medicine, Jinan Central Hospital, Shandong University, Jinan, 250013, People's Republic of China
- Research Center of Basic Medicine, Central Hospital Affiliated to Shandong First Medical University, Jinan, 250013, People's Republic of China
| | - Muhua Luan
- Research Center of Basic Medicine, Jinan Central Hospital, Shandong University, Jinan, 250013, People's Republic of China
- Research Center of Basic Medicine, Central Hospital Affiliated to Shandong First Medical University, Jinan, 250013, People's Republic of China
| | - Wenshuai Zhu
- Research Center of Basic Medicine, Central Hospital Affiliated to Shandong First Medical University, Jinan, 250013, People's Republic of China
| | - Yuanxin Xing
- Research Center of Basic Medicine, Jinan Central Hospital, Shandong University, Jinan, 250013, People's Republic of China
- Research Center of Basic Medicine, Central Hospital Affiliated to Shandong First Medical University, Jinan, 250013, People's Republic of China
| | - Xiaoli Ma
- Research Center of Basic Medicine, Jinan Central Hospital, Shandong University, Jinan, 250013, People's Republic of China
- Research Center of Basic Medicine, Central Hospital Affiliated to Shandong First Medical University, Jinan, 250013, People's Republic of China
| | - Yunshan Wang
- Research Center of Basic Medicine, Jinan Central Hospital, Shandong University, Jinan, 250013, People's Republic of China
- Research Center of Basic Medicine, Central Hospital Affiliated to Shandong First Medical University, Jinan, 250013, People's Republic of China
| | - Yanfei Jia
- Department of Medical Laboratory, Shandong Second Medical University, Weifang, 261053, People's Republic of China.
- Research Center of Basic Medicine, Jinan Central Hospital, Shandong University, Jinan, 250013, People's Republic of China.
- Research Center of Basic Medicine, Central Hospital Affiliated to Shandong First Medical University, Jinan, 250013, People's Republic of China.
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Wang Y, Liu C, Chen H, Jiao X, Wang Y, Cao Y, Li J, Zhang X, Sun Y, Zhuo N, Dong F, Gao M, Wang F, Dong L, Gong J, Sun T, Zhu W, Zhang H, Shen L, Lu Z. Clinical efficacy and identification of factors confer resistance to afatinib (tyrosine kinase inhibitor) in EGFR-overexpressing esophageal squamous cell carcinoma. Signal Transduct Target Ther 2024; 9:153. [PMID: 38937446 PMCID: PMC11211462 DOI: 10.1038/s41392-024-01875-4] [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: 11/22/2023] [Revised: 05/13/2024] [Accepted: 05/20/2024] [Indexed: 06/29/2024] Open
Abstract
Epidermal growth factor receptor (EGFR) is reportedly overexpressed in most esophageal squamous cell carcinoma (ESCC) patients, but anti-EGFR treatments offer limited survival benefits. Our preclinical data showed the promising antitumor activity of afatinib in EGFR-overexpressing ESCC. This proof-of-concept, phase II trial assessed the efficacy and safety of afatinib in pretreated metastatic ESCC patients (n = 41) with EGFR overexpression (NCT03940976). The study met its primary endpoint, with a confirmed objective response rate (ORR) of 39% in 38 efficacy-evaluable patients and a median overall survival of 7.8 months, with a manageable toxicity profile. Transcriptome analysis of pretreatment tumors revealed that neurotrophic receptor tyrosine kinase 2 (NTRK2) was negatively associated with afatinib sensitivity and might serve as a predictive biomarker, irrespective of EGFR expression. Notably, knocking down or inhibiting NTRK2 sensitized ESCC cells to afatinib treatment. Our study provides novel findings on the molecular factors underlying afatinib resistance and indicates that afatinib has the potential to become an important treatment for metastatic ESCC patients.
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Affiliation(s)
- Yanni Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, Beijing, China
| | - Chang Liu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, Beijing, China
| | - Huan Chen
- Genecast Biotechnology Co., Ltd, Wuxi, PR China
| | - Xi Jiao
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, Beijing, China
| | - Yujiao Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, Beijing, China
| | - Yanshuo Cao
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, Beijing, China
| | - Jian Li
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, Beijing, China
| | - Xiaotian Zhang
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, Beijing, China
| | - Yu Sun
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Pathology, Peking University Cancer Hospital and Institute, Beijing, China
| | - Na Zhuo
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, Beijing, China
| | - Fengxiao Dong
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, Beijing, China
| | - Mengting Gao
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, Beijing, China
| | - Fengyuan Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, Beijing, China
| | - Liyuan Dong
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, Beijing, China
| | - Jifang Gong
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, Beijing, China
| | - Tianqi Sun
- Precision Scientific (Beijing) Co., Ltd., Beijing, China
| | - Wei Zhu
- Generulor Company Bio-X Lab, Zhuhai, Guangdong, China
| | - Henghui Zhang
- Biomedical Innovation Center, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.
- Beijing Key Laboratory for Therapeutic Cancer Vaccines, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.
| | - Lin Shen
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, Beijing, China.
| | - Zhihao Lu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, Beijing, China.
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Ogura N, Yamamoto S, Kato K. Progress in second-line antibody therapies for advanced esophageal squamous cell carcinoma. Expert Opin Biol Ther 2024; 24:503-509. [PMID: 38860728 DOI: 10.1080/14712598.2024.2366493] [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: 12/21/2023] [Accepted: 06/06/2024] [Indexed: 06/12/2024]
Abstract
INTRODUCTION The prognosis of advanced esophageal squamous cell carcinoma (ESCC) is poor. Although cytotoxic drugs have been widely used in advanced ESCC, several antibody agents have recently been reported to be effective. AREAS COVERED Nivolumab and pembrolizumab are anti-PD-1 antibodies that improve immunosuppression by binding to programmed death-1 (PD-1), leading to an antitumor effect. Randomized phase III trials have found these immune checkpoint inhibitors (ICIs) to be effective as second-line treatment. ATTRACTION-3, which compared nivolumab monotherapy with taxane monotherapy in patients with previously treated advanced ESCC, reported prolonged overall survival in the nivolumab group. KEYNOTE-181 found that overall survival was longer in patients with PD-L1-positive ESCC who received second-line treatment with pembrolizumab than in those who received chemotherapy. Sym004 and amivantamab are antibodies that target the epidermal growth factor receptor and have demonstrated efficacy in the treatment of other tumors in recent phase I studies. Furthermore, clinical trials on antibody-drug conjugates such as enfortumab vedotin and DS-7300 for solid tumors are currently ongoing. EXPERT OPINION The standard first-line treatments for patients with advanced ESCC contain ICIs. Therefore, drugs with different mechanisms of action that can overcome resistance to ICIs are needed as second-line or later-line treatments to improve clinical outcomes in these patients.
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Affiliation(s)
- Nozomu Ogura
- Department of Head and Neck, Esophageal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Shun Yamamoto
- Department of Head and Neck, Esophageal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Ken Kato
- Department of Head and Neck, Esophageal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan
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Kato K, Doki Y, Chau I, Xu J, Wyrwicz L, Motoyama S, Ogata T, Kawakami H, Hsu C, Adenis A, El Hajbi F, Di Bartolomeo M, Braghiroli MI, Holtved E, Makino T, Blum Murphy M, Amaya‐Chanaga C, Patel A, Hu N, Matsumura Y, Kitagawa Y, Ajani J. Nivolumab plus chemotherapy or ipilimumab versus chemotherapy in patients with advanced esophageal squamous cell carcinoma (CheckMate 648): 29-month follow-up from a randomized, open-label, phase III trial. Cancer Med 2024; 13:e7235. [PMID: 38716626 PMCID: PMC11077338 DOI: 10.1002/cam4.7235] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2023] [Revised: 02/29/2024] [Accepted: 04/21/2024] [Indexed: 05/12/2024] Open
Abstract
BACKGROUND First-line nivolumab plus chemotherapy and nivolumab plus ipilimumab both demonstrated significant overall survival (OS) benefit versus chemotherapy in previously untreated patients with advanced esophageal squamous cell carcinoma (ESCC) in the CheckMate 648 trial, leading to approvals of both nivolumab-containing regimens in many countries. We report longer-term follow-up data. METHODS This open-label, phase III trial (NCT03143153) enrolled adults with previously untreated, unresectable, advanced, recurrent, or metastatic ESCC. Patients were randomized 1:1:1 to nivolumab plus chemotherapy, nivolumab plus ipilimumab, or chemotherapy. Primary endpoints were OS and progression-free survival (PFS) by blinded independent central review. Hierarchical testing was performed first in patients with tumor cell programmed death ligand 1 (PD-L1) expression of ≥1% and then in the overall population. RESULTS A total of 970 patients were randomly assigned. After 29 months of minimum follow-up, nivolumab plus chemotherapy continued to demonstrate improvement in OS versus chemotherapy (hazard ratio [HR] = 0.59 [95% CI: 0.46-0.76]) in patients with tumor cell PD-L1 expression of ≥1% and in the overall population (HR = 0.78 [95% CI: 0.65-0.93]) and with nivolumab plus ipilimumab versus chemotherapy (HR = 0.62 [95% CI: 0.48-0.80]) in patients with tumor cell PD-L1 expression of ≥1% and in the overall population (HR = 0.77 [95% CI: 0.65-0.92]). In patients with tumor cell PD-L1 expression of ≥1%, nivolumab plus chemotherapy demonstrated PFS benefit versus chemotherapy (HR = 0.67 [95% CI: 0.51-0.89]); PFS benefit was not observed with nivolumab plus ipilimumab versus chemotherapy (HR = 1.04 [95% CI: 0.79-1.36]). Among all treated patients (n = 936), Grade 3-4 treatment-related adverse events were reported in 151 (49%, nivolumab plus chemotherapy), 105 (32%, nivolumab plus ipilimumab), and 110 (36%, chemotherapy) patients. CONCLUSIONS Nivolumab plus chemotherapy and nivolumab plus ipilimumab continued to demonstrate clinically meaningful OS benefit versus chemotherapy with no new safety signals identified with longer follow-up, further supporting use as first-line standard treatment options for patients with advanced ESCC.
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Affiliation(s)
- Ken Kato
- Department of Head and Neck, Esophageal Medical OncologyNational Cancer Center HospitalTokyoJapan
| | - Yuichiro Doki
- Osaka University Graduate School of MedicineOsakaJapan
| | - Ian Chau
- Royal Marsden HospitalLondon & SurreyUK
| | - Jianming Xu
- Department of Gastrointestinal OncologyThe Fifth Medical Center of the PLA General HospitalBeijingChina
| | - Lucjan Wyrwicz
- Klinika Onkologii i RadioterapiiNarodowy Instytut OnkologiiWarszawaPoland
| | | | | | | | | | | | | | | | | | | | - Tomoki Makino
- Osaka University Graduate School of MedicineOsakaJapan
| | | | | | | | - Nan Hu
- Bristol Myers SquibbPrincetonNew JerseyUSA
| | | | | | - Jaffer Ajani
- The University of Texas MD Anderson Cancer CenterHoustonTexasUSA
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10
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Li J, Xu C, Yuan S. A cost-effectiveness analysis of the combination of serplulimab with chemotherapy for advanced esophageal squamous cell carcinoma: insights from the ASTRUM-007 trial. COST EFFECTIVENESS AND RESOURCE ALLOCATION 2024; 22:8. [PMID: 38281053 PMCID: PMC10821310 DOI: 10.1186/s12962-024-00516-5] [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: 11/22/2023] [Accepted: 01/17/2024] [Indexed: 01/29/2024] Open
Abstract
BACKGROUND Combined serplulimab and chemotherapy demonstrated improved clinical survival outcomes in patients with advanced esophageal squamous cell carcinoma (ESCC) and PD-L1 combined positive scores (CPS) ≥ 1. The present study aimed to evaluate the economic viability of integrating serplulimab in combination with chemotherapy as a potential therapeutic approach for treating ESCC in China. METHODS A Markov model was constructed to evaluate the economic and health-related implications of combining serplulimab with chemotherapy. With the incremental cost-effectiveness ratio (ICER), costs and results in terms of health were estimated. For assessing parameter uncertainty, one-way and probabilistic sensitivity studies were carried out. RESULTS The combination of serplulimab and chemotherapy yielded incremental costs and QALYs of $3,163 and 0.14, $2,418 and 0.10, and $3,849 and 0.15, respectively, for the overall population as well as patients with PD-L1 CPS1-10 and PD-L1 CPS ≥ 10. This corresponds to ICER values per QALY of $23,657, $23,982, and $25,134. At the prespecified WTP limit, the probabilities of serplulimab with chemotherapy being the preferred intervention option were 74.4%, 61.3%, and 78.1% for the entire patient population, those with PD-L1 1 ≤ CPS < 10, and those with PD-L1 CPS ≥ 10, respectively. The stability of the presented model was confirmed through sensitivity studies. CONCLUSIONS In conclusion, the combination of Serplulimab and chemotherapy showed excellent cost-effectiveness compared to chemotherapy alone in treating PD-L1-positive patients with ESCC in China.
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Affiliation(s)
- Jiahui Li
- Department of Radiation Oncology, Kexin Cancer Hospital, Changsha, 410000, China.
| | - Chaoqun Xu
- Department of Radiation Oncology, Kexin Cancer Hospital, Changsha, 410000, China
| | - Suyun Yuan
- Department of Radiation Oncology, Kexin Cancer Hospital, Changsha, 410000, China
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Liu Q, Chen J, Lin Y, Ye J, Shen W, Luo H, Li B, Huang W, Wei S, Song J, Wang Y, Yang H, Lai S, Zhu H, Ai D, Chen Y, Deng J, Hao S, Zhao K. Systemic therapy with or without local intervention for oligometastatic oesophageal squamous cell carcinoma (ESO-Shanghai 13): an open-label, randomised, phase 2 trial. Lancet Gastroenterol Hepatol 2024; 9:45-55. [PMID: 37980921 DOI: 10.1016/s2468-1253(23)00316-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2023] [Revised: 09/12/2023] [Accepted: 09/12/2023] [Indexed: 11/21/2023]
Abstract
BACKGROUND The efficacy of local therapy for patients with oligometastatic oesophageal squamous cell carcinoma is unclear. We aimed to assess the efficacy of local plus systemic therapy compared with systemic therapy alone in patients with oligometastatic oesophageal squamous cell carcinoma. METHODS The ESO-Shanghai 13 trial was a randomised, open-label, multicentre, phase 2 trial. Patients (aged ≥18 years) were recruited from six hospitals in China with histological confirmation of oligometastatic oesophageal squamous cell carcinoma with a controlled primary tumour and one to four metastatic lesions. Eligible patients were randomly assigned via a computer-generated schedule in a 1:1 ratio to receive either systemic therapy alone (ie, systemic therapy only group) or combined systemic and local therapy (ie, systemic and local therapy group). The systemic therapy regimens in both groups were at the discretion of the investigator and included chemotherapy alone, anti-PD-1 antibodies alone, or chemotherapy plus anti-PD-1 antibodies. Local therapy-radiotherapy, surgery, or thermal ablation-was delivered to all metastatic lesions for patients in the systemic and local therapy group. Randomisation was balanced dynamically on three factors: the number of disease sites, the lines of systemic therapy, and the location of the metastases. Patients and investigators were not masked to treatment allocation. The primary endpoint was progression-free survival, defined as the time from randomisation to progression or death from any cause in the intention-to-treat population. The safety population included all patients who had undergone random assignment and at least one of the intended therapies. This trial is registered with ClinicalTrials.gov, NCT03904927. The trial is ongoing but closed to new participants. FINDINGS 116 patients were screened for enrolment between March 5, 2019, and Sept 16, 2021, and 104 patients who met the eligibility criteria were randomly assigned to the systemic and local therapy group (n=53) or the systemic therapy only group (n=51). 20 (38%) patients in the systemic plus local therapy group and 23 (45%) patients in the systemic therapy only group received anti-PD-1 antibody-based systemic therapy; three patients in the systemic and local therapy group did not receive systemic therapy. At a median follow-up of 30·5 months (IQR 24·7-37·8), median progression-free survival was 15·3 months (95% CI 10·1-20·5) in the systemic and local therapy group versus 6·4 months (5·2-7·6) in the systemic therapy only group (stratified hazard ratio 0·26 [95% CI 0·16-0·42]; stratified log rank p<0·0001). Grade 1-2 acute oesophagitis was more common in the systemic and local therapy group than in the systemic therapy only group (10 [19%] vs one [2%] patients; p=0·036). The number of patients who had grade 3 or worse treatment-related adverse events was similar between groups (25 [47%] vs 21 [41%]; p=0·538), with the most common adverse events being leukocytopenia (17 [32%] vs 18 [35%]) and neutropenia (19 [36%] vs 20 [39%]). Treatment-related deaths occurred in two patients in the systemic and local therapy group and one patient in the systemic therapy only group. INTERPRETATION The addition of local treatment for metastases could significantly improve progression-free survival among patients with oligometastatic oesophageal squamous cell carcinoma being treated with systemic therapy. Our findings suggest that combining local and systemic therapy could be a treatment option for patients with oligometastatic oesophageal squamous cell carcinoma, but further support from phase 3 trials is required. FUNDING Science and Technology Commission of Shanghai Municipality, National Nature Science Foundation of China, and Shanghai Municipal Health Commission. TRANSLATION For the Chinese translation of the abstract see Supplementary Materials section.
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Affiliation(s)
- Qi Liu
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; Shanghai Clinical Research Center for Radiation Oncology, Shanghai Key Laboratory of Radiation Oncology, Shanghai, China
| | - Junqiang Chen
- Department of Radiation Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China
| | - Yu Lin
- Department of Radiation Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China
| | - Jinjun Ye
- Department of Radiation Oncology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China
| | - Wenbin Shen
- Radiotherapy Department of Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Honglei Luo
- Department of Radiation Oncology, Huai'an First People's Hospital, Huai'an, China
| | - Baosheng Li
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
| | - Wei Huang
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
| | - Shihong Wei
- Department of Radiation Oncology, Gansu Province Cancer Hospital, Lanzhou, China
| | - Jibin Song
- State Key Laboratory of Chemical Resource Engineering, College of Chemistry, Beijing University of Chemical Technology Department, Beijing, China
| | - Yaohui Wang
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; Department of Intervention Therapy, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Huanjun Yang
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; Shanghai Clinical Research Center for Radiation Oncology, Shanghai Key Laboratory of Radiation Oncology, Shanghai, China
| | - Songtao Lai
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; Shanghai Clinical Research Center for Radiation Oncology, Shanghai Key Laboratory of Radiation Oncology, Shanghai, China
| | - Hongcheng Zhu
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; Shanghai Clinical Research Center for Radiation Oncology, Shanghai Key Laboratory of Radiation Oncology, Shanghai, China
| | - Dashan Ai
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; Shanghai Clinical Research Center for Radiation Oncology, Shanghai Key Laboratory of Radiation Oncology, Shanghai, China
| | - Yun Chen
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; Shanghai Clinical Research Center for Radiation Oncology, Shanghai Key Laboratory of Radiation Oncology, Shanghai, China
| | - Jiaying Deng
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; Shanghai Clinical Research Center for Radiation Oncology, Shanghai Key Laboratory of Radiation Oncology, Shanghai, China
| | - Shengnan Hao
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; Shanghai Clinical Research Center for Radiation Oncology, Shanghai Key Laboratory of Radiation Oncology, Shanghai, China
| | - Kuaile Zhao
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; Shanghai Clinical Research Center for Radiation Oncology, Shanghai Key Laboratory of Radiation Oncology, Shanghai, China.
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Nian Z, Zhao Q, He Y, Xie R, Liu W, Chen T, Huang S, Dong L, Huang R, Yang L. Efficacy and Safety of First-line Therapies for Advanced Unresectable Oesophageal Squamous Cell Cancer: a Systematic Review and Network Meta-analysis. Clin Oncol (R Coll Radiol) 2024; 36:30-38. [PMID: 37827946 DOI: 10.1016/j.clon.2023.09.011] [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: 06/15/2023] [Revised: 08/27/2023] [Accepted: 09/21/2023] [Indexed: 10/14/2023]
Abstract
AIM To compare the clinical efficacy and safety of first-line treatments for advanced unresectable oesophageal squamous cell cancer. MATERIALS AND METHODS A systematic review and network meta-analysis was carried out by retrieving and retaining relevant literature from databases. The studies were randomised controlled trials comparing first-line treatments for advanced unresectable oesophageal squamous cell cancer. A Bayesian network meta-analysis was used to assess clinical outcomes. RESULTS Nine studies including 4499 patients receiving first-line treatments were analysed. For all populations, toripalimab plus chemotherapy tended to provide the best overall survival (hazard ratio 0.58, 95% confidence intervals 0.43-0.78) and sintilimab plus chemotherapy provided the best progression-free survival (0.56, 0.46-0.68). Nivolumab plus chemotherapy presented the best objective response rate (odds ratio 2.45, 1.78-3.42) and camrelizumab plus chemotherapy (0.47, 0.29-0.74) appeared to be the safest. Sintilimab plus chemotherapy (0.55, 0.40-0.75) and nivolumab (0.54, 0.37-0.80) plus chemotherapy had the best overall survival in programmed death ligand 1 (PD-L1) tumour proportion score <1% and ≥1% subgroups. Toripalimab plus chemotherapy (0.61, 0.40-0.93) and pembrolizumab (0.57, 0.43-0.75) were the best in overall survival in combined positive score <10 and ≥10 subgroups, respectively. Toripalimab plus chemotherapy showed the best overall survival in the Asian group; pembrolizumab presented better overall survival in the Asian population than the non-Asian group. CONCLUSION Most immunotherapy combined with chemotherapy showed superior clinical benefits and sintilimab plus chemotherapy, toripalimab plus chemotherapy and tislelizumab plus chemotherapy had better comprehensive clinical efficacy. PD-L1 expression detection and ethnicity differences are still of great significance and most suitable regimens varied from each subgroup.
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Affiliation(s)
- Z Nian
- School of Pharmacy, Fujian Medical University, Fuzhou, China
| | - Q Zhao
- Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China
| | - Y He
- School of Pharmacy, Fujian Medical University, Fuzhou, China
| | - R Xie
- Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China
| | - W Liu
- Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China
| | - T Chen
- Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China
| | - S Huang
- Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China
| | - L Dong
- Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China
| | - R Huang
- Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China
| | - L Yang
- Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China.
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13
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Gao Z, Huang S, Wang S, Tang D, Xu W, Zeng R, Qiao G. Efficacy and safety of immunochemotherapy, immunotherapy, chemotherapy, and targeted therapy as first-line treatment for advanced and metastatic esophageal cancer: a systematic review and network meta-analysis. THE LANCET REGIONAL HEALTH. WESTERN PACIFIC 2023; 38:100841. [PMID: 37457900 PMCID: PMC10339186 DOI: 10.1016/j.lanwpc.2023.100841] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 03/17/2023] [Revised: 05/22/2023] [Accepted: 06/21/2023] [Indexed: 07/18/2023]
Abstract
Background The treatment of esophageal cancer has entered a new phase with the development of immunotherapy. The current investigation purpose is to investigate and contrast the efficacy and safety of immunotherapy, immunochemotherapy, chemotherapy, and targeted therapy as first-line treatment for individuals suffering from advanced and metastatic esophageal cancer. Methods Within the framework of this systematic review and network meta-analysis, clinical trials published or reported in English up until 01 May, 2022, were retrieved from Embase, PubMed, Cochrane Central Register of Controlled Trials, the ClinicalTrials.gov databases, ESMO, and ASCO. The analysis incorporated randomized controlled trials (RCTs) from phase 2 to 3 that evaluated a minimum of two first-line therapeutic regimens for metastatic esophageal cancer were included in the analysis. The primary outcomes were overall survival (OS) and progression-free survival (PFS). Secondary clinical outcomes included the incidence of objective response rate (ORR), and adverse events (AEs) of any grade and ≥3 grade. Relative summary data were extracted from included studies by GZ, HS, WS, and TD. For clear statistical analysis, chemotherapy was divided into two categories of fluorouracil-based chemotherapy (FbCT) and fluorouracil-free chemotherapy (FfCT). Bayesian frequentist approach was employed to conduct the network meta-analysis. The indirect intercomparison between regimens was presented with league tables (HRs and 95% CI for OS and PFS, ORs and 95% CI for ORR and AEs). A greater surface value under the cumulative ranking (SUCRA) indicates a higher potential ranking for the corresponding treatment. A further calculation of relative results about esophageal squamous cell cancer was performed in the subgroup analysis. The current protocol for the systematic review has been properly registered on PROSPERO (registration number: CRD42021241145). Findings The final analysis comprised 17 trials that involved 9128 patients and 19 distinct treatment regimens. Within the scope of investigated immunotherapy (IO) combinations, toripalimab + FfCT (tori + FfCT) demonstrated the best OS advantages (tori + FfCT vs. FbCT, HR 0.57, 95% CI 0.38-0.85; tori + FfCT vs. FfCT, HR 0.58, 95% CI 0.43-0.78). In terms of PFS, camrelizumab + FfCT (cam + FfCT) demonstrated the best PFS advantages (FbCT vs. cam + FfCT, HR 1.79, 95% CI 1.22-2.63; FfCT vs. cam + FfCT, HR 1.79, 95% CI 1.47-2.17). Nivolumab + FbCT (nivo + FbCT vs. FfCT, OR 3.29, 95% CI 1.43-7.56) showed the best objective responses. Compared to the conventional chemotherapy regimen, the toxicity was observed to be the slightest for the tori + FfCT (FbCT vs. tori + FfCT, OR 3.07, 95% CI 1.22-7.7) and sintilimab + FfCT (FbCT vs. sin + FfCT, OR 2.93, 95% CI 1.16-7.37). The results in this study were evaluated as having a low heterogeneity since the I2 value was ≤25% in all analyses. Interpretation Compared to foreign IO combinations, sin + FfCT, tori + FfCT, cam + FfCT, and tisle + FbCT are superior first-line treatment options for patients with advanced and metastatic esophageal cancer. Although foreign IO combinations, such as pembro + FbCT and nivo + FbCT obtained better objective response rates than other IO combinations, the addition of chemotherapy to IO worsens the safety profiles. Our findings could provide complementary evidence for current guideline recommendations. Funding This work was supported by a grant from the Science and Technology Program of Guangzhou, China (202206010103); and Natural Science Foundation of Guangdong Province (2022A1515012469).
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Affiliation(s)
- Zhen Gao
- Department of Thoracic Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
- Centre of Cancer Cell and Molecular Biology, Barts Cancer Institute, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London, UK
| | - Shujie Huang
- Department of Thoracic Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
| | - Sichao Wang
- Department of Thoracic Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
- Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
- Department of Clinical Oncology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - Dezhao Tang
- Department of Thoracic Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
| | - Wei Xu
- School of Public Health, Chongqing Medical University, Chongqing, China
| | - Ruijie Zeng
- Department of Gastroenterology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
| | - Guibin Qiao
- Department of Thoracic Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
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14
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Cheng M, Xin Q, Ma S, Ge M, Wang F, Yan X, Jiang B. Advances in the Theranostics of Oesophageal Squamous Carcinoma. ADVANCED THERAPEUTICS 2023; 6. [DOI: 10.1002/adtp.202200251] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2022] [Indexed: 01/04/2025]
Abstract
AbstractOesophageal squamous carcinoma (ESCC) is one of the most lethal human malignancies, and it is a more aggressive form of oesophageal cancer (EC) that comprises over 90% of all EC cases in China compared with oesophageal adenocarcinoma (EAC). The high mortality of ESCC is attributed to the late‐stage diagnosis, chemoradiotherapy resistance, and lack of appropriate therapeutic targets and corresponding therapeutic formulations. Recently, emerging clinical and translational investigations have involved genome analyses, diagnostic biomarkers, and targeted therapy for ESCC, and these studies provide a new horizon for improving the clinical outcomes of patients with ESCC. Here, the latest research advances in the theranostics of ESCC are reviewed and the unique features of ESCC (including differences from EAC, genomic alterations, and microbe infections), tissue and circulating biomarkers, chemoradiotherapy resistance, clinical targeted therapy for ESCC, identification of novel therapeutic targets, and designation of nanotherapeutic systems for ESCC are particularly focused on. Finally, the perspectives for future clinical and translational theranostic research of ESCC are discussed and the obstacles that must be overcome in ESCC theranostics are described.
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Affiliation(s)
- Miaomiao Cheng
- Nanozyme Medical Center School of Basic Medical Sciences Zhengzhou University Zhengzhou 450001 China
| | - Qi Xin
- Nanozyme Medical Center School of Basic Medical Sciences Zhengzhou University Zhengzhou 450001 China
| | - Saiyu Ma
- Nanozyme Medical Center School of Basic Medical Sciences Zhengzhou University Zhengzhou 450001 China
| | - Mengyue Ge
- Nanozyme Medical Center School of Basic Medical Sciences Zhengzhou University Zhengzhou 450001 China
| | - Feng Wang
- Oncology Department The First Affiliated Hospital of Zhengzhou University Zhengzhou Henan 450000 China
| | - Xiyun Yan
- Nanozyme Medical Center School of Basic Medical Sciences Zhengzhou University Zhengzhou 450001 China
- State Key Laboratory of Esophageal Cancer Prevention &Treatment Zhengzhou Henan 450001 China
- CAS Engineering Laboratory for Nanozyme Key Laboratory of Protein and Peptide Pharmaceuticals Institute of Biophysics Chinese Academy of Sciences Beijing 100101 China
| | - Bing Jiang
- Nanozyme Medical Center School of Basic Medical Sciences Zhengzhou University Zhengzhou 450001 China
- State Key Laboratory of Esophageal Cancer Prevention &Treatment Zhengzhou Henan 450001 China
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15
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Lorenzen S, Schwarz A, Pauligk C, Goekkurt E, Stocker G, Knorrenschild JR, Illerhaus G, Dechow T, Moehler M, Moulin JC, Pink D, Stahl M, Schaaf M, Goetze TO, Al-Batran SE. Ramucirumab plus irinotecan / leucovorin / 5-FU versus ramucirumab plus paclitaxel in patients with advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction, who failed one prior line of palliative chemotherapy: the phase II/III RAMIRIS study (AIO-STO-0415). BMC Cancer 2023; 23:561. [PMID: 37337155 PMCID: PMC10278289 DOI: 10.1186/s12885-023-11004-z] [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: 02/15/2022] [Accepted: 05/23/2023] [Indexed: 06/21/2023] Open
Abstract
BACKGROUND Paclitaxel in combination with ramucirumab is the standard of care second-line therapy in gastro-esophageal adenocarcinoma (GEA). As the number of taxane pretreated patients in the perioperative or first-line setting is increasing, it is unknown whether these patients benefit from re-applying a taxane in using the combination of paclitaxel and ramucirumab. Furthermore, the rates of neurotoxicity with first-line FOLFOX or FLOT range from 30%-70%, making second-line taxane-containing therapy less suitable to a meaningful portion of patients. This patient group is likely to benefit from a taxane-free second-line chemotherapy regimen, such as FOLFIRI and ramucirumab (FOLFIRI-Ram). Therefore, the RAMIRIS phase III trial evaluates the effects of the regimen of FOLFIRI-Ram in the second-line treatment after a taxane-based chemotherapy in patients with advanced GEA. METHODS The RAMIRIS trial is a randomized, open-label, multicenter phase II/III study comparing treatment of FOLFIRI-Ram (arm A) with paclitaxel and ramucirumab (arm B). The Phase II is already closed with 111 enrolled patients. In the phase III, 318 taxane-pretreated patients with advanced GEA will be recruited and randomized 1:1 to FOLFIRI (5-FU 2400 mg/m2 over 46 h i.v., irinotecan 180 mg/m2 i.v.; 5-FU 400 mg/m2 bolus; leucovorin 400 mg/m2 i.v.; on day 1 and 15, q28) with ramucirumab 8 mg/kg every two weeks (Arm A) or paclitaxel 80 mg/m2 (days 1, 8, 15, q28) with ramucirumab 8 mg/kg every two weeks (Arm B). The primary endpoints are overall survival (OS) and objective overall response rate (ORR). Secondary endpoints are progression-free survival (PFS), disease control rate and safety and quality of life as assessed by EORTC-QLQ-C30 questionnaire. DISCUSSION The already completed RAMIRIS phase II demonstrated feasibility and efficacy of FOLFIRI-Ram. Especially docetaxel-pretreated patients seemed to markedly benefit from FOLFIRI-Ram, with favorable response- and PFS rates and lower toxicity. This offers a rationale for the phase III trial. If the RAMIRIS III trial transfers and confirms the results, they will affect the current treatment guidelines, recommending the combination therapy of FOLFIRI-Ram for taxane-pretreated patients with advanced GEA. TRIAL REGISTRATION NCT03081143 Date of registration: 13.11.2015.
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Affiliation(s)
- Sylvie Lorenzen
- Klinikum rechts der Isar, Technische Universität München, III. Medizinische Klinik und Poliklinik, München, Germany.
| | - Alix Schwarz
- Klinikum rechts der Isar, Technische Universität München, III. Medizinische Klinik und Poliklinik, München, Germany
| | - Claudia Pauligk
- Institut für Klinische Krebsforschung IKF GmbH am Krankenhaus Nordwest, Frankfurt/Main, Germany
| | - Eray Goekkurt
- Hämatologisch-Onkologische Praxis Eppendorf (HOPE), und Universitäres Cancer Center Hamburg (UCCH), Hamburg, Germany
| | - Gertraud Stocker
- Universitäres Krebszentrum Leipzig (UCCL), Klinik und Poliklinik für Onkologie, Gastroenterologie, Hepatologie, Pneumologie und Infektiologie - Bereich Onkologie Leipzig, Leipzig, Germany
| | - Jorge Riera Knorrenschild
- Universitätsklinikum Marburg, Klinik für Innere Medizin, Hämatologie, Onkologie und Immunologie, Marburg, Germany
| | - Gerald Illerhaus
- Klinikum Stuttgart, Klinik für Hämatologie, Onkologie und Palliativmedizin, Stuttgart, Germany
| | - Tobias Dechow
- Studienzentrum Onkologie Ravensburg, Ravensburg, Germany
| | - Markus Moehler
- I. Department of Internal Medicine, University Cancer Center Mainz, Mainz, Germany
| | - Jean-Charles Moulin
- Ortenau Klinikum Lahr, Medizinische Klinik, Sektion Hämatologie/Onkologie, Lahr, Germany
| | - Daniel Pink
- Klinik und Poliklinik für Innere Medizin C, Hämatologie und Onkologie, Transplantationszentrum, Palliativmedizin, Universität Greifswald, Greifswald, and Klinik für Hämatologie, Onkologie und Palliativmedizin, Sarkomzentrum Berlin-Brandenburg, HELIOS Klinikum Bad-Saarow, Bad Saarow, Germany
| | - Michael Stahl
- Evang. Kliniken Essen-Mitte, Klinik für Internistische Onkologie und Hämatologie, Essen, Germany
| | - Marina Schaaf
- Institut für Klinische Krebsforschung IKF GmbH am Krankenhaus Nordwest, Frankfurt/Main, Germany
| | - Thorsten Oliver Goetze
- Institut für Klinische Krebsforschung IKF GmbH am Krankenhaus Nordwest, Frankfurt/Main, Germany
- University Cancer Center Frankfurt, Krankenhaus Nordwest, Institut für Klinisch-Onkologische Forschung, Frankfurt/Main, Germany
| | - Salah-Eddin Al-Batran
- Institut für Klinische Krebsforschung IKF GmbH am Krankenhaus Nordwest, Frankfurt/Main, Germany
- University Cancer Center Frankfurt, Krankenhaus Nordwest, Institut für Klinisch-Onkologische Forschung, Frankfurt/Main, Germany
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16
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Chen TH, Chen MH, Hung YP, Chiang NJ, Huang KH, Lin YH, Lin RW, Chao Y, Li AFY, Yu HY, Hwang HE, Yeh YC, Wang YC, Fang WL. Elevated PD-L1 Expression and Microsatellite Instability in Elderly Patients With Gastric Cancer. J Immunother 2023; 46:111-119. [PMID: 36809276 DOI: 10.1097/cji.0000000000000458] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2022] [Accepted: 01/25/2023] [Indexed: 02/23/2023]
Abstract
Immunotherapy in combination with chemotherapy is the current treatment of choice for frontline programmed cell death ligand 1 (PD-L1)-positive gastric cancer. However, the best treatment strategy remains an unmet medical need for elderly or fragile patients with gastric cancer. Previous studies have revealed that PD-L1 expression, Epstein-Barr virus association, and microsatellite instability-high (MSI-H) are the potential predictive biomarkers for immunotherapy use in gastric cancer. In this study, we showed that PD-L1 expression, tumor mutation burden, and the proportion of MSI-H were significantly elevated in elderly patients with gastric cancer who were older than 70 years compared with patients younger than 70 years from analysis of The Cancer Genome Atlas gastric adenocarcinoma cohort [≥70/<70: MSI-H: 26.8%/15.0%, P =0.003; tumor mutation burden: 6.7/5.1 Mut/Mb, P =0.0004; PD-L1 mRNA: 5.6/3.9 counts per million mapped reads, P =0.005]. In our real-world study, 416 gastric cancer patients were analyzed and showed similar results (≥70/<70: MSI-H: 12.5%/6.6%, P =0.041; combined positive score ≥1: 38.1%/21.5%, P <0.001). We also evaluated 16 elderly patients with gastric cancer treated with immunotherapy and revealed an objective response of 43.8%, a median overall survival of 14.8 months, and a median progression-free survival of 7.0 months. Our research showed that a durable clinical response could be expected when treating elderly patients with gastric cancer with immunotherapy, and this approach is worth further study.
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Affiliation(s)
- Tien-Hua Chen
- Division of Medical Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan
- Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Ming-Huang Chen
- Division of Medical Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan
- Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Center for Immuno-Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Yi-Ping Hung
- Division of Medical Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan
- Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Center for Immuno-Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Nai-Jung Chiang
- Division of Medical Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan
- National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan
| | - Kuo-Hung Huang
- Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Yi-Hsiang Lin
- Institute of Biomedical Informatics, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Ryan Weihsiang Lin
- Institute of Biomedical Informatics, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Yee Chao
- Division of Medical Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan
- Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Center for Immuno-Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Anna Fen-Yau Li
- Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Department of Pathology, and Laboratory Medicine Taipei Veterans General Hospital, Taipei, Taiwan
| | - Hung-Yuan Yu
- Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- Hospitalist ward, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Hsuen-En Hwang
- Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Yi-Chen Yeh
- Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Institute of Biomedical Informatics, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Department of Pathology, and Laboratory Medicine Taipei Veterans General Hospital, Taipei, Taiwan
| | - Yu-Chao Wang
- Institute of Biomedical Informatics, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Wen-Liang Fang
- Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
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17
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Kawazoe T, Ito S, Ohgaki K, Fujinaka Y, Funakoshi H, Otake A, Wang H, Morita K, Fushimi F, Ikeda Y. Successful conversion surgery following chemotherapy with an immune checkpoint inhibitor in an older adult patient with stage IVB esophageal squamous cell carcinoma: a case report. Surg Case Rep 2023; 9:51. [PMID: 36995570 PMCID: PMC10063768 DOI: 10.1186/s40792-023-01634-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2023] [Accepted: 03/24/2023] [Indexed: 03/31/2023] Open
Abstract
BACKGROUND Chemotherapy and chemoradiotherapy are common treatments for esophageal squamous cell carcinoma with distant metastasis; however, the prognosis remains poor, and complete remission is difficult to achieve. Here, we report a case of an older adult patient with esophageal squamous cell carcinoma who underwent surgery following combined treatment of immunotherapy and chemotherapy and achieved pathological complete response. CASE PRESENTATION An 80-year-old woman presenting with difficulty swallowing was referred to our hospital. She was diagnosed with esophageal squamous cell carcinoma with distant metastasis of the lymph node at the dorsal side of the IVC and the left supraclavicular lymph node. She was treated with pembrolizumab, cisplatin, and 5-fluorouracil. After four pharmacotherapy courses, primary tumor and metastatic lymph node shrinkage was observed. The patient underwent thoracoscopic subtotal esophagectomy and regional lymph node dissection. The lymph node at the dorsal side of the IVC was not resected, and the left supraclavicular lymph node was removed. Histological examination revealed complete response with no residual tumor or lymph node metastasis. The patient had no recurrence 10 months postoperatively without adjuvant chemotherapy. CONCLUSIONS Conversion surgery following preoperative therapy, including immunotherapy, may be an effective treatment strategy for improving survival in patients with esophageal squamous cell carcinoma even among older adult patients.
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Affiliation(s)
- Tetsuro Kawazoe
- Department of Gastrointestinal Surgery, Kyushu Central Hospital of the Mutual Aid Association of Public School Teachers, 3-23-1 Shiobaru, Minami-Ku, Fukuoka-City, Fukuoka, 815-8588, Japan.
| | - Shuhei Ito
- Department of Gastrointestinal Surgery, Kyushu Central Hospital of the Mutual Aid Association of Public School Teachers, 3-23-1 Shiobaru, Minami-Ku, Fukuoka-City, Fukuoka, 815-8588, Japan
| | - Kippei Ohgaki
- Department of Gastrointestinal Surgery, Kyushu Central Hospital of the Mutual Aid Association of Public School Teachers, 3-23-1 Shiobaru, Minami-Ku, Fukuoka-City, Fukuoka, 815-8588, Japan
| | - Yoshihiko Fujinaka
- Department of Gastrointestinal Surgery, Kyushu Central Hospital of the Mutual Aid Association of Public School Teachers, 3-23-1 Shiobaru, Minami-Ku, Fukuoka-City, Fukuoka, 815-8588, Japan
| | - Hiroki Funakoshi
- Department of Gastrointestinal Surgery, Kyushu Central Hospital of the Mutual Aid Association of Public School Teachers, 3-23-1 Shiobaru, Minami-Ku, Fukuoka-City, Fukuoka, 815-8588, Japan
| | - Akihiko Otake
- Department of Gastrointestinal Surgery, Kyushu Central Hospital of the Mutual Aid Association of Public School Teachers, 3-23-1 Shiobaru, Minami-Ku, Fukuoka-City, Fukuoka, 815-8588, Japan
| | - Huanlin Wang
- Department of Gastrointestinal Surgery, Kyushu Central Hospital of the Mutual Aid Association of Public School Teachers, 3-23-1 Shiobaru, Minami-Ku, Fukuoka-City, Fukuoka, 815-8588, Japan
| | - Kazutoyo Morita
- Department of Gastrointestinal Surgery, Kyushu Central Hospital of the Mutual Aid Association of Public School Teachers, 3-23-1 Shiobaru, Minami-Ku, Fukuoka-City, Fukuoka, 815-8588, Japan
| | - Fumiyoshi Fushimi
- Department of Pathology, Kyushu Central Hospital of the Mutual Aid Association of Public School Teachers, Fukuoka, Japan
| | - Yoichi Ikeda
- Department of Gastrointestinal Surgery, Kyushu Central Hospital of the Mutual Aid Association of Public School Teachers, 3-23-1 Shiobaru, Minami-Ku, Fukuoka-City, Fukuoka, 815-8588, Japan
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18
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Kitagawa Y, Ishihara R, Ishikawa H, Ito Y, Oyama T, Oyama T, Kato K, Kato H, Kawakubo H, Kawachi H, Kuribayashi S, Kono K, Kojima T, Takeuchi H, Tsushima T, Toh Y, Nemoto K, Booka E, Makino T, Matsuda S, Matsubara H, Mano M, Minashi K, Miyazaki T, Muto M, Yamaji T, Yamatsuji T, Yoshida M. Esophageal cancer practice guidelines 2022 edited by the Japan esophageal society: part 1. Esophagus 2023:10.1007/s10388-023-00993-2. [PMID: 36933136 PMCID: PMC10024303 DOI: 10.1007/s10388-023-00993-2] [Citation(s) in RCA: 161] [Impact Index Per Article: 80.5] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Accepted: 02/27/2023] [Indexed: 03/19/2023]
Affiliation(s)
- Yuko Kitagawa
- Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-Ku, Tokyo, 160-8582, Japan.
| | - Ryu Ishihara
- Department of Gastrointestinal Oncology, Osaka International Cancer Institute, Osaka, Japan
| | - Hitoshi Ishikawa
- QST Hospital, National Institutes for Quantum Science and Technology, Chiba, Japan
| | - Yoshinori Ito
- Department of Radiation Oncology, Showa University School of Medicine, Tokyo, Japan
| | - Takashi Oyama
- Department of Hepato-Biliary-Pancreatic and Gastrointestinal Surgery, International University of Health and Welfare School of Medicine, Chiba, Japan
| | - Tsuneo Oyama
- Department of Endoscopy, Saku Central Hospital Advanced Care Center, Nagano, Japan
| | - Ken Kato
- Department Head and Neck, Esophageal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan
| | | | - Hirofumi Kawakubo
- Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-Ku, Tokyo, 160-8582, Japan
| | - Hiroshi Kawachi
- Department of Pathology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Shiko Kuribayashi
- Department of Gastroenterology and Hepatology, Gunma University Graduate School of Medicine, Gunma, Japan
| | - Koji Kono
- Department of Gastrointestinal Tract Surgery, Fukushima Medical University, Fukushima, Japan
| | - Takashi Kojima
- Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Chiba, Japan
| | - Hiroya Takeuchi
- Department of Surgery, Hamamatsu University School of Medicine, Shizuoka, Japan
| | - Takahiro Tsushima
- Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan
| | - Yasushi Toh
- National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan
| | - Kenji Nemoto
- Department of Radiology, Yamagata University Graduate School of Medicine, Yamagata, Japan
| | - Eisuke Booka
- Department of Surgery, Hamamatsu University School of Medicine, Shizuoka, Japan
| | - Tomoki Makino
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Satoru Matsuda
- Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-Ku, Tokyo, 160-8582, Japan
| | - Hisahiro Matsubara
- Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Masayuki Mano
- Department of Central Laboratory and Surgical Pathology, National Hospital Organization Osaka National Hospital, Osaka, Japan
| | - Keiko Minashi
- Clinical Trial Promotion Department, Chiba Cancer Center, Chiba, Japan
| | - Tatsuya Miyazaki
- Department of Surgery, Japanese Red Cross Maebashi Hospital, Gunma, Japan
| | - Manabu Muto
- Department of Clinical Oncology, Kyoto University Hospital, Kyoto, Japan
| | - Taiki Yamaji
- Division of Epidemiology, National Cancer Center Institute for Cancer Control, Tokyo, Japan
| | - Tomoki Yamatsuji
- Department of General Surgery, Kawasaki Medical School, Okayama, Japan
| | - Masahiro Yoshida
- Department of Hepato-Biliary-Pancreatic and Gastrointestinal Surgery, School of Medicine, International University of Health and Welfare Ichikawa Hospital, Chiba, Japan
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19
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Li D, Tang L, Hu J, Cao X, He Y. Immune checkpoint inhibitors' combination therapy as first-line treatment in advanced esophageal squamous cell carcinoma: a meta-analysis. J Cancer Res Clin Oncol 2023; 149:933-939. [PMID: 35751682 DOI: 10.1007/s00432-022-04066-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2022] [Accepted: 05/11/2022] [Indexed: 10/17/2022]
Abstract
PURPOSE The benefit of immune checkpoint inhibitors' (ICIs) combination therapy in patients with advanced esophageal squamous cell carcinoma (ESCC) remained unclear. We performed a meta-analysis to explore the efficacy and safety of ICIs' combination therapy versus chemotherapy alone as first-line treatment in advanced ESCC. METHODS A systematic review of randomized controlled trials (RCTs) of ICIs' combination therapy as first-line treatment in advanced ESCC was conducted via searching PubMed, Embase, and Cochrane database. The data for efficacy and safety of ICIs' combination therapy were subject to meta-analysis. Subgroup analysis was performed in patients with different PD-L1 expression status. RESULTS A total of 5 RCTs and 3163 patients were included. Overall, the hazard ratio (HR) for overall survival (OS) benefit with ICIs' combination therapy was 0.68 (95% CI 0.62-0.75) compared with chemotherapy alone. The HR for progression-free survival (PFS) benefit and the odds ratio (OR) for overall response rate (ORR) increase were 0.62 (95% CI 0.56-0.68) and 2.01 (95% CI 1.70-2.38), respectively. The OS and PFS benefits with ICIs' combination therapy over chemotherapy alone were also observed in the subgroup of PD-L1 positive expression, but not in the subgroup of PD-L1 negative expression. The incidence of grade 3 or higher treatment-related adverse events was 60.4% with ICIs' combination therapy and 56.3% with chemotherapy alone (OR, 1.19; 95% CI 0.90-1.57). CONCLUSION ICIs' combination therapy showed superior OS, PFS, and ORR over chemotherapy alone with a manageable safety profile. These results suggested that ICIs' combination therapy can be considered as a new first-line treatment for advanced ESCC.
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Affiliation(s)
- Dianhe Li
- Department of Oncology, Panyu Central Hospital, No. 8 Fuyu Road East, Panyu, Guangzhou, Guangdong, People's Republic of China
| | - Ling Tang
- Department of Otolaryngology-Head and Neck Surgery, Panyu Central Hospital, Guangzhou, People's Republic of China
| | - Jiazhu Hu
- Department of Oncology, Panyu Central Hospital, No. 8 Fuyu Road East, Panyu, Guangzhou, Guangdong, People's Republic of China
| | - Xiaolong Cao
- Department of Oncology, Panyu Central Hospital, No. 8 Fuyu Road East, Panyu, Guangzhou, Guangdong, People's Republic of China
| | - Yan He
- Department of Oncology, Panyu Central Hospital, No. 8 Fuyu Road East, Panyu, Guangzhou, Guangdong, People's Republic of China.
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20
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Ooki A, Osumi H, Chin K, Watanabe M, Yamaguchi K. Potent molecular-targeted therapies for advanced esophageal squamous cell carcinoma. Ther Adv Med Oncol 2023; 15:17588359221138377. [PMID: 36872946 PMCID: PMC9978325 DOI: 10.1177/17588359221138377] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2022] [Accepted: 10/21/2022] [Indexed: 01/15/2023] Open
Abstract
Esophageal cancer (EC) remains a public health concern with a high mortality and disease burden worldwide. Esophageal squamous cell carcinoma (ESCC) is a predominant histological subtype of EC that has unique etiology, molecular profiles, and clinicopathological features. Although systemic chemotherapy, including cytotoxic agents and immune checkpoint inhibitors, is the main therapeutic option for recurrent or metastatic ESCC patients, the clinical benefits are limited with poor prognosis. Personalized molecular-targeted therapies have been hampered due to the lack of robust treatment efficacy in clinical trials. Therefore, there is an urgent need to develop effective therapeutic strategies. In this review, we summarize the molecular profiles of ESCC based on the findings of pivotal comprehensive molecular analyses, highlighting potent therapeutic targets for establishing future precision medicine for ESCC patients, with the most recent results of clinical trials.
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Affiliation(s)
- Akira Ooki
- Department of Gastroenterological Chemotherapy,
Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31
Ariake, Koto-ku, Tokyo 135-8550, Japan
| | - Hiroki Osumi
- Department of Gastroenterological Chemotherapy,
Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo,
Japan
| | - Keisho Chin
- Department of Gastroenterological Chemotherapy,
Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo,
Japan
| | - Masayuki Watanabe
- Department of Gastroenterological Surgery,
Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo,
Japan
| | - Kensei Yamaguchi
- Department of Gastroenterological Chemotherapy,
Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo,
Japan
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21
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Li Y, Ji Y, Shen L, Yin X, Huang T, Deng B, Guo H, Wu Y, Chen Y. Clinical efficacy of combination therapy of an immune checkpoint inhibitor with taxane plus platinum versus an immune checkpoint inhibitor with fluorouracil plus platinum in the first-line treatment of patients with locally advanced, metastatic, or recurrent esophageal squamous cell carcinoma. Front Oncol 2022; 12:1015302. [PMID: 36605427 PMCID: PMC9808083 DOI: 10.3389/fonc.2022.1015302] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2022] [Accepted: 10/25/2022] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Chemotherapy combined with immune checkpoints inhibitors (ICIs) has been established as a standard treatment for locally advanced, metastatic, or recurrent esophageal squamous cell cancer (ESCC). However, the optimal chemotherapy regimen in combination therapy is still unclear. PURPOSE To investigate the efficacy and adverse events of the fluorouracil plus platinum (FP) and taxane plus platinum (TP) regimens in ESCC patients receiving chemo-immunotherapy, we conducted this systematic review and meta-analysis. METHODS Potentially eligible studies were searched from Medline, Embase, Web of Science, and the Cochrane Library. Pooled rates of overall response rate (ORR), disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and adverse events were compared between ICIs+TP and ICIs+FP groups in ESCC patients receiving first-line chemo-immunotherapy. RESULTS A total of 10 clinical trials were included, of which 5 were randomized controlled trials. Compared with chemotherapy alone, chemo-immunotherapy significantly improved the OS of ESCC patients (pooled HR=0.69; 95% CI, 0.63-0.76; p<0.01). Pooled analysis revealed that ESCC patients receiving ICIs+TP had significantly higher ORR, DCR, PFS, and OS rates than those receiving ICIs+FP. No statistically significant difference in the pooled incidence rate of treatment-related death was found (2.3% vs 0.9%, P=0.08). ICIs+TP had significantly higher rates of hematologic toxicity but lower rates of gastrointestinal toxicity than ICIs+FP. CONCLUSIONS Based on the current data, the first-line treatment using ICIs+TP may be a better option than ICIs+FP in advanced, metastatic, or recurrent ESCC.
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Affiliation(s)
- Ying Li
- Department of Radio-Chemotherapy, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, China
| | - Yanyan Ji
- Department of Radio-Chemotherapy, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, China
| | - Lin Shen
- Department of Radio-Chemotherapy, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, China
| | - Xudong Yin
- Department of Radio-Chemotherapy, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, China
| | - Tianyu Huang
- Department of Radio-Chemotherapy, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, China
| | - Bin Deng
- Department of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, China
| | - Hong Guo
- Department of Thoracic Surgery, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, China
| | - Yunjiang Wu
- Department of Thoracic Surgery, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, China
| | - Yong Chen
- Department of Radio-Chemotherapy, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, China
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22
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Nagata Y, Yamamoto S, Kato K. Immune checkpoint inhibitors in esophageal cancer: Clinical development and perspectives. Hum Vaccin Immunother 2022; 18:2143177. [PMID: 36375821 PMCID: PMC9746438 DOI: 10.1080/21645515.2022.2143177] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2022] [Revised: 10/11/2022] [Accepted: 10/31/2022] [Indexed: 11/16/2022] Open
Abstract
Esophageal cancer is the sixth most common cause of cancer-related mortality worldwide. The standard treatment for unresectable esophageal cancer is systemic chemotherapy. However, the survival benefit is limited, with a median overall survival of less than 10 months. The advent of immune checkpoint inhibitors (ICIs), including programmed cell death-1 antibodies, has revolutionized the treatment paradigm for esophageal cancer. Since demonstrating promising efficacy with manageable safety in several clinical trials, ICIs has finally reached the point where they can be used in various tumor stages in the clinical setting. ICIs are most promising treatments that can be expected to improve the prognosis in patients with esophageal cancer now and in the future. This review outlines the mechanisms, results of clinical trials, and prospects for future studies of ICIs in esophageal cancer. It also discusses clinical questions and challenges in the therapeutic development of ICIs.
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Affiliation(s)
- Yusuke Nagata
- Department of Gastroenterology, Nagano Municipal Hospital, Nagano, Japan
| | - Shun Yamamoto
- Department of Head and Neck, Esophageal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Ken Kato
- Department of Head and Neck, Esophageal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan
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23
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Obermannová R, Alsina M, Cervantes A, Leong T, Lordick F, Nilsson M, van Grieken NCT, Vogel A, Smyth EC. Oesophageal cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol 2022; 33:992-1004. [PMID: 35914638 DOI: 10.1016/j.annonc.2022.07.003] [Citation(s) in RCA: 295] [Impact Index Per Article: 98.3] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2022] [Revised: 07/08/2022] [Accepted: 07/11/2022] [Indexed: 12/12/2022] Open
Affiliation(s)
- R Obermannová
- Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Faculty of Medicine, Masaryk University, Brno, Czech Republic
| | - M Alsina
- Department of Medical Oncology, Hospital Universitario de Navarra (HUN), Pamplona; Gastrointestinal Tumours Group, Vall d'Hebron Institute of Oncology, Barcelona
| | - A Cervantes
- Department of Medical Oncology, INCLIVA Biomedical Research Institute, University of Valencia, Valencia; CIBERONC, Instituto de Salud Carlos III, Madrid, Spain
| | - T Leong
- The Sir Peter MacCallum Department of Oncology, Peter MacCallum Cancer Centre, University of Melbourne, Melbourne, Australia
| | - F Lordick
- Department of Medicine II (Oncology, Gastroenterology, Hepatology, Pulmonology and Infectious Diseases), University Cancer Center Leipzig (UCCL), Leipzig University Medical Center, Leipzig, Germany
| | - M Nilsson
- Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm; Department of Upper Abdominal Diseases, Karolinska University Hospital, Stockholm, Sweden
| | - N C T van Grieken
- Department of Pathology, Amsterdam University Medical Centers, Cancer Center Amsterdam, Vrije Universiteit, Amsterdam, The Netherlands
| | - A Vogel
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - E C Smyth
- Department of Oncology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
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24
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Abstract
Esophageal squamous cell carcinoma (ESCC) is common in the developing world with decreasing incidence in developed countries and carries significant morbidity and mortality. Major risk factors for ESCC development include significant use of alcohol and tobacco. Screening for ESCC can be recommended in high-risk populations living in highly endemic regions. The treatment of ESCC ranges from endoscopic resection therapy or surgery in localized disease to chemoradiotherapy in metastatic disease, and prognosis is directly related to the stage at diagnosis. New immunotherapies and molecular targeted therapies may improve the dismal survival outcomes in patients with metastatic ESCC.
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Affiliation(s)
- D Chamil Codipilly
- Division of Gastroenterology and Hepatology, Mayo Clinic, SMH Campus, 6 Alfred GI Unit, 200 1st Street South West, Rochester MN 55905, USA
| | - Kenneth K Wang
- Division of Gastroenterology and Hepatology, Mayo Clinic, SMH Campus, 6 Alfred GI Unit, 200 1st Street South West, Rochester MN 55905, USA.
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Hu J, Chen Z, Lv J, Zheng Z, Bei Y, Chen X, Zheng L, Song W, Xu Y. The Application of Nimotuzumab Combined With Definitive Chemoradiotherapy Toward the Treatment of Locally Advanced Cervical Esophageal Carcinoma: A Retrospective Study. Front Oncol 2022; 12:905422. [PMID: 35898885 PMCID: PMC9310542 DOI: 10.3389/fonc.2022.905422] [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: 04/20/2022] [Accepted: 06/07/2022] [Indexed: 11/25/2022] Open
Abstract
Objective To evaluate the safety and effectiveness of nimotuzumab in combination with chemoradiotherapy for locally advanced cervical esophageal squamous cell carcinoma. Methods Retrospective analysis was conducted from September 2012 to February 2017 among 50 locoregional-advanced cervical esophageal carcinoma (CEC) patients who received concurrent chemoradiotherapy (CRT) combined with or without nimotuzumab at Ningbo Medical Center Lihuili Hospital. Intensity-modulated radiotherapy (IMRT) was administrated on all patients. All patients were divided into two groups, of which 26 (Group A) received 200 mg (22 of 50) or 400 mg (4 of 50) of nimotuzumab per week with CRT and 24 (Group B) received definitive CRT. Results The median follow-up time was 23 months. The median overall survival (OS) and progression-free survival (PFS) were 40.6 and 21.1 months for all, respectively. The 1-, 2-, and 3-year OS rates on the whole were 79.6%, 62.1%, and 47.8%. There was no statistical difference in overall response rate and disease control rate between the two groups. Patients treated with nimotuzumab (group A) had better PFS than the definitive CRT group (group B) (P < 0.05). However, the median OS was 41.4 months in group A and 32.4 months in group B, respectively (P = 0.517). Multivariate analysis showed that PFS among those with lower Eastern Cooperative Oncology Group (ECOG) score (HR = 5.11; P < 0.01), stage II (HR = 9.52; P < 0.01) and the application of nimotuzumab combined with CRT (HR = 0.16; P < 0.01) was much longer. Furthermore, ECOG, stage, C-reactive protein (CRP) baseline, and histological grade can also be used as independent predictors of OS. Grade >3 adverse reactions were not observed. The most common adverse event related to nimotuzumab was mild fever and the occurrence rate was 19% (5 of 26). The incidence of anemia was 65.4% in group A and 87.5% in group B (P < 0.05). Conclusions For locoregional-advanced CEC, nimotuzumab combined with IMRT and concomitant chemotherapy was tolerated and effective. In addition, patients with a normal pretherapeutic serum CRP level (CRP < 10 mg/L) can achieve better OS.
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Affiliation(s)
- Jing Hu
- Department of Radiation Oncology, Ningbo Medical Center Lihuili Hospital, Ningbo, China
| | - Zhe Chen
- Department of Thoracic Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo, China
| | - Jiaming Lv
- Department of Radiation Oncology, Ningbo Medical Center Lihuili Hospital, Ningbo, China
| | - Zhen Zheng
- Department of Radiation Oncology, Ningbo Medical Center Lihuili Hospital, Ningbo, China
| | - Yanping Bei
- Department of Radiation Oncology, Ningbo Medical Center Lihuili Hospital, Ningbo, China
| | - Xue Chen
- Department of Radiation Oncology, Ningbo Medical Center Lihuili Hospital, Ningbo, China
| | - Lu Zheng
- Department of Radiation Oncology, Ningbo Medical Center Lihuili Hospital, Ningbo, China
| | - Wenjie Song
- Department of Thoracic Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo, China
| | - Yunbao Xu
- Department of Radiotherapy and Chemotherapy, Hwamei Hospital, University of Chinese Academy of Sciences, Ningbo, China
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Thyroid Dysfunction as a Predictive Indicator in Camrelizumab of Advanced Esophageal Squamous Cell Carcinoma. J Immunol Res 2022; 2022:4015897. [PMID: 35832645 PMCID: PMC9273411 DOI: 10.1155/2022/4015897] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Accepted: 05/26/2022] [Indexed: 12/23/2022] Open
Abstract
Thyroid dysfunction (TD) induced by programmed death-1 (PD-1) or programmed cell death-ligand 1 (PD-L1) immune checkpoint inhibitors (ICIs) has been widely reported. However, the effects of ICI-induced TD on the survival of patients with esophageal squamous cell carcinoma (ESCC) have not been described. Herein, a retrospective study was conducted, which 82 patients with advanced metastatic or recurrent ESCC treated with camrelizumab were enrolled. Twenty patients (24.4%) experienced TD during camrelizumab treatment with or without chemotherapy. The median onset time of TD was 1.7 months. The incidence of TD was 35.6% in patients who previously received thoracic radiotherapy versus 10.8% in patients who did not (P =0.009). Patients with TD had significantly longer median progression-free survival (5.5 months vs 3.5 months, P =0.035) and overall survival (26.7 months vs 11.5 months, P <0.001). TD is frequently observed in ESCC patients treated with camrelizumab and especially in patients who received radiotherapy previously. ESCC patients with TD during ICIs treatment often have better prognosis.
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Paclitaxel and Cisplatin with or without Cetuximab in metastatic esophageal squamous cell carcinoma: A randomized, multicenter, open-label Phase II trial. Innovation (N Y) 2022; 3:100239. [PMID: 35509869 PMCID: PMC9059084 DOI: 10.1016/j.xinn.2022.100239] [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: 12/14/2021] [Accepted: 04/04/2022] [Indexed: 12/24/2022] Open
Abstract
Lack of effective targeted therapy in metastatic esophageal squamous cell carcinoma (ESCC) underscores the urgent need for identifying new treatment approaches for this challenging disease. We sought to assess the addition of cetuximab to paclitaxel-cisplatin chemotherapy for first-line treatment in patients with metastatic ESCC. In this randomized, multicenter, open-label, phase II clinical trial, patients were randomized to receive paclitaxel-cisplatin (TP) (paclitaxel [175 mg/m2 intravenously (i.v.) on day 1 of every 3-week cycle] and cisplatin [75 mg/m2 i.v. on day 1 of every 3-week cycle]) and TP plus cetuximab (CTP) (cetuximab, 400 mg/m2 i.v. on day 1 of week 1, followed by 250 mg/m2 weekly), respectively. Targeted next-generation sequencing (NGS) was performed on 89 tumor samples for biomarker exploration. The primary endpoint was progression-free survival (PFS) in the intention-to-treat population. With a median follow-up of 22.6 months, median PFS was 5.7 months (95% confidence interval [CI]: 4.8–7.0) in patients administered CTP versus 4.2 months (95% CI: 3.0–5.3) in the TP group (hazard ratio [HR] = 0.61; 95% CI: 0.40–0.93; p = 0.02). Median overall survival was 11.5 months (95% CI: 7.9–13.1) in the CTP group and 10.5 months (95% CI: 9.0–13.2) in the TP arm (HR = 0.98; 95% CI: 0.67–1.44; p = 0.91). The most common reported greater than or equal to grade 3 adverse events were neutropenia (35.2% versus 22.4%) and leukopenia (25.4% versus 13.2%). In patients with epidermal growth factor receptor (EGFR) amplification tumors (15.7%), PFS was improved with CTP compared with TP treatment (HR = 0.11; 95% CI: 0.01–0.98; p = 0.018). First-line CTP significantly improves PFS, with a manageable safety profile in patients with metastatic ESCC.
Compare the effect of Cetuximab + chemotherapy with chemotherapy alone in ESCC CTP regimen improves progression-free survival with a manageable safety profile ESCC patients with EGFR amplification obtain greater therapeutic benefit from CTP CTP regimen represents a new treatment option for ESCC
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Zhou J, Wu Z, Zhang Z, Goss L, McFarland J, Nagaraja A, Xie Y, Gu S, Peng K, Zeng Y, Zhang X, Long H, Nakagawa H, Rustgi A, Diehl JA, Meyerson M, Wong KK, Bass A. Pan-ERBB kinase inhibition augments CDK4/6 inhibitor efficacy in oesophageal squamous cell carcinoma. Gut 2022; 71:665-675. [PMID: 33789967 PMCID: PMC8921580 DOI: 10.1136/gutjnl-2020-323276] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2020] [Revised: 03/11/2021] [Accepted: 03/18/2021] [Indexed: 02/05/2023]
Abstract
OBJECTIVE Oesophageal squamous cell carcinoma (OSCC), like other squamous carcinomas, harbour highly recurrent cell cycle pathway alterations, especially hyperactivation of the CCND1/CDK4/6 axis, raising the potential for use of existing CDK4/6 inhibitors in these cancers. Although CDK4/6 inhibition has shown striking success when combined with endocrine therapy in oestrogen receptor positive breast cancer, CDK4/6 inhibitor palbociclib monotherapy has not revealed evidence of efficacy to date in OSCC clinical studies. Herein, we sought to elucidate the identification of key dependencies in OSCC as a foundation for the selection of targets whose blockade could be combined with CDK4/6 inhibition. DESIGN We combined large-scale genomic dependency and pharmaceutical screening datasets with preclinical cell line models, to identified potential combination therapies in squamous cell cancer. RESULTS We identified sensitivity to inhibitors to the ERBB family of receptor kinases, results clearly extending beyond the previously described minority of tumours with EGFR amplification/dependence, specifically finding a subset of OSCCs with dual dependence on ERBB3 and ERBB2. Subsequently. we demonstrated marked efficacy of combined pan-ERBB and CDK4/6 inhibition in vitro and in vivo. Furthermore, we demonstrated that squamous lineage transcription factor KLF5 facilitated activation of ERBBs in OSCC. CONCLUSION These results provide clear rationale for development of combined ERBB and CDK4/6 inhibition in these cancers and raises the potential for KLF5 expression as a candidate biomarker to guide the use of these agents. These data suggested that by combining existing Food and Drug Administration (FDA)-approved agents, we have the capacity to improve therapy for OSCC and other squamous cancer.
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Affiliation(s)
- Jin Zhou
- Department of Surgery, West China Hospital, Sichuan University, Chendu, Sichuan Province, China
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
| | - Zhong Wu
- Department of Surgery, West China Hospital, Sichuan University, Chendu, Sichuan Province, China
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
| | - Zhouwei Zhang
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
- Cancer Program, Broad Institute, Cambridge, Massachusetts, USA
| | - Louisa Goss
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
| | - James McFarland
- Cancer Program, Broad Institute, Cambridge, Massachusetts, USA
| | - Ankur Nagaraja
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
| | - Yingtian Xie
- Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Shengqing Gu
- Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA, USA
- Department of Data Science, Dana Farber Cancer Institute, Boston, MA, USA
- Department of Biostatistics, Harvard T.H.Chan School of Public Health, Boston, MA, USA
| | - Ke Peng
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
| | - Yong Zeng
- Department of Surgery, West China Hospital, Sichuan University, Chendu, Sichuan Province, China
| | - Xiaoyang Zhang
- Department of Oncologic Sciences, Huntsman Cancer Institute; University of Utah, Salt Lake City, Utah, USA
| | - Henry Long
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
- Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Hiroshi Nakagawa
- Division of Digestive and Liver Diseases, Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA
- Herbert Irving Comprehensive Cancer Center, Columbia University Vagelos College of Physicians and Surgeons, New York, New York, USA
| | - Anil Rustgi
- Division of Digestive and Liver Diseases, Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA
- Herbert Irving Comprehensive Cancer Center, Columbia University Vagelos College of Physicians and Surgeons, New York, New York, USA
| | - J Alan Diehl
- Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio, USA
| | - Matthew Meyerson
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
- Cancer Program, Broad Institute, Cambridge, Massachusetts, USA
| | - Kwok-Kin Wong
- Division of Hematology and Medical Oncology, New York University Medical Center, New York, New York, USA
| | - Adam Bass
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
- Cancer Program, Broad Institute, Cambridge, Massachusetts, USA
- Herbert Irving Comprehensive Cancer Center, Columbia University Vagelos College of Physicians and Surgeons, New York, New York, USA
- Division of Hematology and Oncology, Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA
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Ajani JA, D'Amico TA, Bentrem DJ, Chao J, Cooke D, Corvera C, Das P, Enzinger PC, Enzler T, Fanta P, Farjah F, Gerdes H, Gibson MK, Hochwald S, Hofstetter WL, Ilson DH, Keswani RN, Kim S, Kleinberg LR, Klempner SJ, Lacy J, Ly QP, Matkowskyj KA, McNamara M, Mulcahy MF, Outlaw D, Park H, Perry KA, Pimiento J, Poultsides GA, Reznik S, Roses RE, Strong VE, Su S, Wang HL, Wiesner G, Willett CG, Yakoub D, Yoon H, McMillian N, Pluchino LA. Gastric Cancer, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2022; 20:167-192. [PMID: 35130500 DOI: 10.6004/jnccn.2022.0008] [Citation(s) in RCA: 902] [Impact Index Per Article: 300.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Gastric cancer is the third leading cause of cancer-related deaths worldwide. Over 95% of gastric cancers are adenocarcinomas, which are typically classified based on anatomic location and histologic type. Gastric cancer generally carries a poor prognosis because it is often diagnosed at an advanced stage. Systemic therapy can provide palliation, improved survival, and enhanced quality of life in patients with locally advanced or metastatic disease. The implementation of biomarker testing, especially analysis of HER2 status, microsatellite instability (MSI) status, and the expression of programmed death-ligand 1 (PD-L1), has had a significant impact on clinical practice and patient care. Targeted therapies including trastuzumab, nivolumab, and pembrolizumab have produced encouraging results in clinical trials for the treatment of patients with locally advanced or metastatic disease. Palliative management, which may include systemic therapy, chemoradiation, and/or best supportive care, is recommended for all patients with unresectable or metastatic cancer. Multidisciplinary team management is essential for all patients with localized gastric cancer. This selection from the NCCN Guidelines for Gastric Cancer focuses on the management of unresectable locally advanced, recurrent, or metastatic disease.
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Affiliation(s)
| | | | - David J Bentrem
- Robert H. Lurie Comprehensive Cancer Center of Northwestern University
| | | | | | | | - Prajnan Das
- The University of Texas MD Anderson Cancer Center
| | - Peter C Enzinger
- Dana-Farber/Brigham and Women's Cancer Center
- Massachusetts General Hospital Cancer Center
| | | | | | - Farhood Farjah
- Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance
| | | | | | | | | | | | - Rajesh N Keswani
- Robert H. Lurie Comprehensive Cancer Center of Northwestern University
| | | | | | - Samuel J Klempner
- Dana-Farber/Brigham and Women's Cancer Center
- Massachusetts General Hospital Cancer Center
| | - Jill Lacy
- Yale Cancer Center/Smilow Cancer Hospital
| | | | | | - Michael McNamara
- Case Comprehensive Cancer Center/University Hospitals Seidman Cancer Center and Cleveland Clinic Taussig Cancer Institute
| | - Mary F Mulcahy
- Robert H. Lurie Comprehensive Cancer Center of Northwestern University
| | | | - Haeseong Park
- Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine
| | - Kyle A Perry
- The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute
| | | | | | - Scott Reznik
- UT Southwestern Simmons Comprehensive Cancer Center
| | - Robert E Roses
- Abramson Cancer Center at the University of Pennsylvania
| | | | | | | | | | | | - Danny Yakoub
- St. Jude Children's Research Hospital/The University of Tennessee Health Science Center
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Wang G, Beeraka NM, Xiao W, Zhang Y, Xue N, Chen G, Liu J, Liu Y. Comparative Clinical Efficacy of 'Concurrent Chemoradiotherapy (CCRT) and Anlotinib' Than CCRT in Patients with Locally Advanced ESCC. Technol Cancer Res Treat 2022; 21:15330338221080939. [PMID: 35235470 PMCID: PMC8894970 DOI: 10.1177/15330338221080939] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2021] [Revised: 01/14/2022] [Accepted: 01/31/2022] [Indexed: 12/24/2022] Open
Abstract
Objective: Radiotherapy or chemoradiotherapy has been preferred as the clinical therapeutic modalities to combat locally advanced esophageal squamous cell carcinoma (ESCC). The aim of this retrospective study is to ascertain combinatorial efficacy of anlotinib with concurrent radiotherapy (CCRT) rather than CCRT alone. Methods: Locally advanced ESCC patients registered between August 2018 to April 2019 in the third People's hospital of Zhengzhou, the First affiliated hospital of Zhengzhou University, Anyang Cancer Hospital, the Affiliated Hospital of Qingdao University were selected for this retrospective study; and these patients segregated into two groups subsequently who received combinatorial regimen with CCRT and anlotinib compared for treatment-related toxicity, response rates, safety, survival outcomes, than CCRT alone. Results: Progression free survival (PFS) was 0.577 (95% CI, 0.333-0.902, P = 0.014); the median overall survival time was 5 months (95% CI, 4.1-7.5) for the CCRT group, whereas 9 months (95% CI, 7.3-18.0) for the group received 'anlotinib with CCRT' (HR = 0.578, 95% CI, 0.337-0.924, P = 0.021). Overall objective response rates were considerable with a statistical difference between the two groups at 6 months (P1 = 0.027, P2 = 0.015) and 12 months (P1 = 0.012, P2 = 0.027). Overall adverse events are mitigated in combinatorial regimen than CCRT alone except the incidence of hypertension, which was higher in 'anlotinib with CCRT' group than CCRT group (P = 0.023). Total 13 patients exhibited hand-foot skin reactions in the group that received anlotinib in combination with CCRT. Anlotinib in combination with CCRT enhanced the overall survival (OS) rates, whereas incidence of treatment-related toxicity is minimized than CCRT alone. Conclusion: Combinatorial regimen of anlotinib with CCRT significantly enhanced clinical efficacy, safety and may benefit for treating the locally advanced ESCC patients.
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Affiliation(s)
- Gang Wang
- Department of Radiation Oncology, Zhengzhou Third People's Hospital & Zhengzhou Cancer Hospital Affiliated to Henan University, Zhengzhou, China
| | - Narasimha M. Beeraka
- Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Department of Human Anatomy, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation
- Center of Excellence in Molecular Biology and Regenerative Medicine (CEMR), Department of Biochemistry, JSS Academy of Higher Education and Research (JSS AHER), Mysuru, Karnataka India
| | - Wenjing Xiao
- Department of Radiation Oncology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Yaowen Zhang
- Department of Radiation Oncology, Anyang Cancer Hospital, The Fourth Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Anyang, China
| | - Nannan Xue
- Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Gongan Chen
- Department of Radiation Oncology, Zhengzhou Third People's Hospital & Zhengzhou Cancer Hospital Affiliated to Henan University, Zhengzhou, China
| | - Junqi Liu
- Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yang Liu
- Department of Radiotherapy, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China
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Phase II study of BKM120 in patients with advanced esophageal squamous cell carcinoma (EPOC1303). Esophagus 2022; 19:702-710. [PMID: 35904643 PMCID: PMC9436835 DOI: 10.1007/s10388-022-00928-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2021] [Accepted: 05/30/2022] [Indexed: 02/03/2023]
Abstract
BACKGROUND PI3K/AKT/mTOR pathway is frequently overactive in esophageal squamous cell carcinoma (ESCC), making it an attractive treatment target. BKM120 is an oral pan-class I PI3K inhibitor with promising activity in several cancers. We prospectively investigated efficacy, safety, and biomarkers of BKM120 in advanced ESCC. We conducted a multicenter phase II study of BKM120 monotherapy in patients with pretreated advanced ESCC. METHODS BKM120 (100 mg/day) was administered orally in a 28-day cycle. The primary end point was disease control rate (DCR). Tumor samples for all patients were collected for gene alteration analysis in a comprehensive genomic profiling assay. RESULTS Of 42 patients enrolled, 20 had stable disease and two had confirmed partial response. One ineligible patient was excluded from the primary analysis, which met the primary end point (DCR 51.2%; 95% confidence interval [CI], 35.1-67.1). In the 42 patients, median progression-free survival and overall survival were 2.3 (95% CI 1.8-3.2) and 9.0 (95% CI 6.5-11.4) months, respectively. Common grade 3 or 4 adverse events were rash, anorexia, hyponatremia, and abnormal hepatic function; profiles of these events in this study were similar to those in previous studies of BKM120 monotherapy. No treatment-related deaths occurred. PI3K pathway activation was observed in patients with good clinical response. CONCLUSIONS BKM120 monotherapy showed promising efficacy and a manageable toxicity profile even in patients with pretreated advanced ESCC. This study showed the potential target PI3K for ESCC, and further confirmatory trial will be necessary to confirm it. Unique ID issued by UMIN: UMIN 000011217.
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Singh D, Dheer D, Samykutty A, Shankar R. Antibody drug conjugates in gastrointestinal cancer: From lab to clinical development. J Control Release 2021; 340:1-34. [PMID: 34673122 DOI: 10.1016/j.jconrel.2021.10.006] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Revised: 10/05/2021] [Accepted: 10/06/2021] [Indexed: 12/15/2022]
Abstract
The antibody-drug conjugates (ADCs) are one the fastest growing biotherapeutics in oncology and are still in their infancy in gastrointestinal (GI) cancer for clinical applications to improve patient survival. The ADC based approach is developed with tumor specific antigen, antibody carrying cytotoxic agents to precisely target and deliver chemotherapeutics at the tumor site. To date, 11 ADCs have been approved by US-FDA, and more than 80 are in the clinical development phase for different oncological indications. However, The ADCs based therapies in GI cancers are still far from having high-efficient clinical outcomes. The limited success of these ADCs and lessons learned from the past are now being used to develop a newer generation of ADC against GI cancers. In this review, we did a comprehensive assessment of the key components of ADCs, including tumor marker, antibody, cytotoxic payload, and linkage strategy, with a focus on technical improvement and some future trends in the pipeline for clinical translation. The various preclinical and clinical ADCs used in gastrointestinal malignancies, their target, composition and bioconjugation, along with preclinical and clinical outcomes, are discussed. The emphasis is also given to new generation ADCs employing novel mAb, payload, linker, and bioconjugation methods are also included.
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Affiliation(s)
- Davinder Singh
- Natural Products and Medicinal Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Jammu 180001, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
| | - Divya Dheer
- Natural Products and Medicinal Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Jammu 180001, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
| | - Abhilash Samykutty
- Stephenson Comprehensive Cancer Center, University of Oklahoma, Oklahoma City, OK 73104, USA.
| | - Ravi Shankar
- Natural Products and Medicinal Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Jammu 180001, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.
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Huang B, Shi H, Gong X, Yu J, Xiao C, Zhou B, Liang Z, Li X. Comparison of efficacy and safety between pembrolizumab combined with chemotherapy and simple chemotherapy in neoadjuvant therapy for esophageal squamous cell carcinoma. J Gastrointest Oncol 2021; 12:2013-2021. [PMID: 34790369 PMCID: PMC8576253 DOI: 10.21037/jgo-21-610] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Accepted: 10/19/2021] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND Immunotherapy can activate the recognition of tumor antigen, build immune memory, and more and more clinical trials have taken the scheme of immunochemotherapy or immunoradiotherapy as a treatment strategy for esophageal squamous cell carcinoma (ESCC). Our objective was to compare the efficacy and safety between pembrolizumab combined with the chemotherapy group and simple chemotherapy in neoadjuvant therapy of ESCC. METHODS Fifty-four ESCC patients with stage II-IVa were enrolled at the Fifth Affiliated Hospital of Sun Yat-sen University between January 2018 and December 2020, including 23 in the pembrolizumab combined with chemotherapy group (combined group), and 31 in the simple chemotherapy group. All patients received radical surgical treatment after two cycles of neoadjuvant therapy. RESULTS The pathological complete response (pCR) and objective response rate (ORR) in the combined group were significantly higher than that of the simple chemotherapy group (30.4% vs. 9.7%, P=0.048; 86.9% vs. 95.7%, P=0.017) as well as the score of tumor regression ≥2 (80.7% vs. 50.0%, P=0.013). And the complete rate of esophagectomy and R0 /R1 resection rate in the two groups were not statistically significant. Otherwise, the incidence of adverse events in the combined group was similar compared with the simple chemotherapy group. CONCLUSIONS Pembrolizumab combined with chemotherapy showed promising activity with a manageable safety profile. And it could offer a potential new neoadjuvant treatment approach for patients with ESCC.
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Affiliation(s)
- Bingjiang Huang
- Department of Thoracic Oncology, The Cancer Center of the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China
| | - Haiyan Shi
- Department of Cardiothoracic Surgery, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China
| | - Xiaohua Gong
- Department of Cardiothoracic Surgery, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China
| | - Jing Yu
- Department of Minimally Invasive Surgery, The Cancer Center of The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China
| | - Caixia Xiao
- Department of Minimally Invasive Surgery, The Cancer Center of The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China
| | - Bin Zhou
- Department of Minimally Invasive Surgery, The Cancer Center of The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China
| | - Zibin Liang
- Department of Thoracic Oncology, The Cancer Center of the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China
| | - Xiaojian Li
- Department of Thoracic Oncology, The Cancer Center of the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China
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Yamamoto S, Kawakami H, Kii T, Hara H, Kawabata R, Kawada J, Takeno A, Matsuyama J, Ueda S, Okita Y, Endo S, Kimura Y, Yanagihara K, Okuno T, Kurokawa Y, Shimokawa T, Satoh T. Randomized phase II study of docetaxel versus paclitaxel in patients with esophageal squamous cell carcinoma refractory to fluoropyrimidine- and platinum-based chemotherapy: OGSG1201. Eur J Cancer 2021; 154:307-315. [PMID: 34311300 DOI: 10.1016/j.ejca.2021.06.035] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2021] [Revised: 06/09/2021] [Accepted: 06/20/2021] [Indexed: 10/20/2022]
Abstract
BACKGROUND There is no standard chemotherapy for esophageal squamous cell carcinoma (ESCC) refractory to first-line fluoropyrimidine- and platinum-based chemotherapy. We therefore performed a randomized, selection-design phase II trial to compare docetaxel (DTX) and paclitaxel (PTX) in this setting. PATIENTS AND METHODS Eligible patients were randomly assigned to receive either DTX (70 mg/m2 on day 1 of each 21-day cycle) or PTX (100 mg/m2 on days 1, 8, 15, 22, 29 and 36 of each 49-day cycle). The primary end-point was overall survival (OS), and secondary end-points included progression-free survival (PFS), time to treatment failure (TTF), response rate (RR) and safety. RESULTS Seventy-eight eligible patients (N = 39 in each group) were included for efficacy analysis. OS was significantly longer in the PTX group than in the DTX group (median, 8.8 versus 7.3 months; hazard ratio [HR], 0.62; P = 0.047). A significant benefit of PTX over DTX was also apparent in PFS (median, 4.4 versus 2.1 months; HR, 0.49; P = 0.002) and TTF (median, 3.8 versus 2.1 months; HR, 0.45; P < 0.001). RR (25.6% versus 7.7%, P = 0.065) were higher in the PTX group than in the DTX group. Compared to the PTX group, neutropenia (28% versus 80%) and leukopenia (28% versus 76%) of grade ≥3 as well as febrile neutropenia (0% vs. 46%, P < 0.0001) occurred more frequently in the DTX group. CONCLUSION PTX showed a significantly better efficacy as well as a more manageable toxicity compared with DTX. CLINICAL TRIAL REGISTRATION UMIN000007940.
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Affiliation(s)
- Sachiko Yamamoto
- Department of Gastrointestinal Oncology, Osaka International Cancer Institute, Osaka, Osaka, 541-8567, Japan.
| | - Hisato Kawakami
- Department of Medical Oncology, Kindai University Faculty of Medicine, Osakasayama, Osaka, 589-8511, Japan.
| | - Takayuki Kii
- Cancer Chemotherapy Center, Osaka Medical and Pharmaceutical University, Takatsuki, Osaka, 569-0801, Japan.
| | - Hiroki Hara
- Department of Gastroenterology, Saitama Cancer Center, Kitaadachi-gun, Saitama, 362-0806, Japan.
| | - Ryohei Kawabata
- Department of Surgery, Osaka Rosai Hospital, Sakai, Osaka, 591-8025, Japan; Department of Surgery, Sakai City Medical Center, Sakai, Osaka, 593-8304, Japan.
| | - Junji Kawada
- Department of Surgery, Osaka General Medical Center, Osaka, Osaka, 558-8558, Japan.
| | - Atsushi Takeno
- Department of Surgery, Kansai Rosai Hospital, Amagasaki, Hyogo, 660-8511, Japan.
| | - Jin Matsuyama
- Department of Surgery, Yao Municipal Hospital, Yao, Osaka, 581-0069, Japan.
| | - Shugo Ueda
- Department of Gastroenterological Surgery and Oncology, Kitano Hospital, Tazuke Kofukai Medical Research Institute, Osaka, Osaka, 530-8480, Japan.
| | - Yoshihiro Okita
- Department of Medical Oncology, Kobe City Medical Center General Hospital, Kobe, Hyogo, 650-0047, Japan; Department of Clinical Oncology, Kagawa University Faculty of Medicine, Kita-gun, Kagawa, 761-0793, Japan.
| | - Shunji Endo
- Department of Gastroenterological Surgery, Higashiosaka City Medical Center, Higashiosaka, Osaka, 578-8588, Japan.
| | - Yutaka Kimura
- Department of Surgery, Sakai City Medical Center, Sakai, Osaka, 593-8304, Japan; Department of Surgery, Kindai University Faculty of Medicine, Osakasayama, Osaka, 589-8511, Japan.
| | - Kazuhiro Yanagihara
- Department of Medical Oncology, Kansai Electric Power Hospital, Osaka, Osaka, 553-0003, Japan.
| | - Tatsuya Okuno
- Division of Gastroenterology, Department of Internal Medicine, Graduate School of Medicine, Kobe University, Kobe, Hyogo, 650-0017, Japan.
| | - Yukinori Kurokawa
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan.
| | - Toshio Shimokawa
- Department of Medical Data Science, Graduate School of Medicine, Wakayama Medical University, Wakayama, Wakayama, 641-8510, Japan.
| | - Taroh Satoh
- Department of Frontier Science for Cancer and Chemotherapy, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan.
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Sun JM, Shen L, Shah MA, Enzinger P, Adenis A, Doi T, Kojima T, Metges JP, Li Z, Kim SB, Cho BC, Mansoor W, Li SH, Sunpaweravong P, Maqueda MA, Goekkurt E, Hara H, Antunes L, Fountzilas C, Tsuji A, Oliden VC, Liu Q, Shah S, Bhagia P, Kato K. Pembrolizumab plus chemotherapy versus chemotherapy alone for first-line treatment of advanced oesophageal cancer (KEYNOTE-590): a randomised, placebo-controlled, phase 3 study. Lancet 2021; 398:759-771. [PMID: 34454674 DOI: 10.1016/s0140-6736(21)01234-4] [Citation(s) in RCA: 839] [Impact Index Per Article: 209.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2021] [Revised: 05/17/2021] [Accepted: 05/18/2021] [Indexed: 12/23/2022]
Abstract
BACKGROUND First-line therapy for advanced oesophageal cancer is currently limited to fluoropyrimidine plus platinum-based chemotherapy. We aimed to evaluate the antitumour activity of pembrolizumab plus chemotherapy versus chemotherapy alone as first-line treatment in advanced oesophageal cancer and Siewert type 1 gastro-oesophageal junction cancer. METHODS We did a randomised, placebo-controlled, double-blind, phase 3 study across 168 medical centres in 26 countries. Patients aged 18 years or older with previously untreated, histologically or cytologically confirmed, locally advanced, unresectable or metastatic oesophageal cancer or Siewert type 1 gastro-oesophageal junction cancer (regardless of PD-L1 status), measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1, and Eastern Cooperative Oncology Group performance status of 0-1, were randomly assigned (1:1) to intravenous pembrolizumab 200 mg or placebo, plus 5-fluorouracil and cisplatin (chemotherapy), once every 3 weeks for up to 35 cycles. Randomisation was stratified by geographical region, histology, and performance status. Patients, investigators, and site staff were masked to group assignment and PD-L1 biomarker status. Primary endpoints were overall survival in patients with oesophageal squamous cell carcinoma and PD-L1 combined positive score (CPS) of 10 or more, and overall survival and progression-free survival in patients with oesophageal squamous cell carcinoma, PD-L1 CPS of 10 or more, and in all randomised patients. This trial is registered with ClinicalTrials.gov, NCT03189719, and is closed to recruitment. FINDINGS Between July 25, 2017, and June 3, 2019, 1020 patients were screened and 749 were enrolled and randomly assigned to pembrolizumab plus chemotherapy (n=373 [50%]) or placebo plus chemotherapy (n=376 [50%]). At the first interim analysis (median follow-up of 22·6 months), pembrolizumab plus chemotherapy was superior to placebo plus chemotherapy for overall survival in patients with oesophageal squamous cell carcinoma and PD-L1 CPS of 10 or more (median 13·9 months vs 8·8 months; hazard ratio 0·57 [95% CI 0·43-0·75]; p<0·0001), oesophageal squamous cell carcinoma (12·6 months vs 9·8 months; 0·72 [0·60-0·88]; p=0·0006), PD-L1 CPS of 10 or more (13·5 months vs 9·4 months; 0·62 [0·49-0·78]; p<0·0001), and in all randomised patients (12·4 months vs 9·8 months; 0·73 [0·62-0·86]; p<0·0001). Pembrolizumab plus chemotherapy was superior to placebo plus chemotherapy for progression-free survival in patients with oesophageal squamous cell carcinoma (6·3 months vs 5·8 months; 0·65 [0·54-0·78]; p<0·0001), PD-L1 CPS of 10 or more (7·5 months vs 5·5 months; 0·51 [0·41-0·65]; p<0·0001), and in all randomised patients (6·3 months vs 5·8 months; 0·65 [0·55-0·76]; p<0·0001). Treatment-related adverse events of grade 3 or higher occurred in 266 (72%) patients in the pembrolizumab plus chemotherapy group versus 250 (68%) in the placebo plus chemotherapy group. INTERPRETATION Compared with placebo plus chemotherapy, pembrolizumab plus chemotherapy improved overall survival in patients with previously untreated, advanced oesophageal squamous cell carcinoma and PD-L1 CPS of 10 or more, and overall survival and progression-free survival in patients with oesophageal squamous cell carcinoma, PD-L1 CPS of 10 or more, and in all randomised patients regardless of histology, and had a manageable safety profile in the total as-treated population. FUNDING Merck Sharp & Dohme.
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Affiliation(s)
- Jong-Mu Sun
- Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea.
| | - Lin Shen
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China
| | - Manish A Shah
- Weill Cornell Medical College, New York City, NY, USA
| | | | - Antoine Adenis
- Institut de Recherche en Cancérologie de Montpellier (IRCM), Inserm, Université Montpellier, ICM, Montpellier, France
| | - Toshihiko Doi
- National Cancer Center Hospital East, Kashiwa, Japan
| | | | - Jean-Philippe Metges
- CHU Brest-Institut de Cancerologie et d'Hematologie ARPEGO Network, Brest, France
| | - Zhigang Li
- Section of Oesophageal Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Sung-Bae Kim
- Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Byoung Chul Cho
- Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea
| | | | - Shau-Hsuan Li
- Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | | | | | - Eray Goekkurt
- Hematology Oncology Practice Eppendorf and University Cancer Center Hamburg, Hamburg, Germany
| | | | - Luis Antunes
- University Hospital of Santa Maria, Federal University of Santa Maria, and Viver Research Center, Santa Maria, Brazil
| | | | | | | | - Qi Liu
- Merck, Kenilworth, NJ, USA
| | | | | | - Ken Kato
- National Cancer Center Hospital, Tokyo, Japan
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Wang DK, Zuo Q, He QY, Li B. Targeted Immunotherapies in Gastrointestinal Cancer: From Molecular Mechanisms to Implications. Front Immunol 2021; 12:705999. [PMID: 34447376 PMCID: PMC8383067 DOI: 10.3389/fimmu.2021.705999] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Accepted: 07/26/2021] [Indexed: 12/12/2022] Open
Abstract
Gastrointestinal cancer is a leading cause of cancer-related mortality and remains a major challenge for cancer treatment. Despite the combined administration of modern surgical techniques and chemoradiotherapy (CRT), the overall 5-year survival rate of gastrointestinal cancer patients in advanced stage disease is less than 15%, due to rapid disease progression, metastasis, and CRT resistance. A better understanding of the mechanisms underlying cancer progression and optimized treatment strategies for gastrointestinal cancer are urgently needed. With increasing evidence highlighting the protective role of immune responses in cancer initiation and progression, immunotherapy has become a hot research topic in the integrative management of gastrointestinal cancer. Here, an overview of the molecular understanding of colorectal cancer, esophageal cancer and gastric cancer is provided. Subsequently, recently developed immunotherapy strategies, including immune checkpoint inhibitors, chimeric antigen receptor T cell therapies, tumor vaccines and therapies targeting other immune cells, have been described. Finally, the underlying mechanisms, fundamental research and clinical trials of each agent are discussed. Overall, this review summarizes recent advances and future directions for immunotherapy for patients with gastrointestinal malignancies.
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Affiliation(s)
| | | | | | - Bin Li
- Ministry of Education (MOE), Key Laboratory of Tumor Molecular Biology and Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, Jinan University, Guangzhou, China
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Kawamoto T, Nakamura N, Saito T, Tonari A, Wada H, Harada H, Kubota H, Nagakura H, Heianna J, Miyazawa K, Yamada K, Tago M, Fushiki M, Nozaki M, Uchida N, Araki N, Sekii S, Kosugi T, Takahashi T, Shikama N. Palliative brachytherapy and external beam radiotherapy for dysphagia from esophageal cancer: a nationwide survey in Japan. Jpn J Clin Oncol 2021; 51:950-955. [PMID: 33624768 DOI: 10.1093/jjco/hyab015] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2020] [Accepted: 01/31/2021] [Indexed: 01/21/2023] Open
Abstract
BACKGROUND International guidelines recommend brachytherapy for patients with dysphagia from esophageal cancer, whereas brachytherapy is infrequently used to palliate dysphagia in some countries. To clarify the availability of palliative treatment for dysphagia from esophageal cancer and explain why brachytherapy is not routinely performed are unknown, this study investigated the use of brachytherapy and external beam radiotherapy for dysphagia from esophageal cancer. METHODS Japanese Radiation Oncology Study Group members completed a survey and selected the treatment that they would recommend for hypothetical cases of dysphagia from esophageal cancer. RESULTS Of the 136 invited facilities, 61 completed the survey (44.9%). Four (6.6%) facilities performed brachytherapy of the esophagus, whereas brachytherapy represented the first-line treatment at three (4.9%) facilities. Conversely, external beam radiotherapy alone and chemoradiotherapy were first-line treatments at 61 and 58 (95.1%) facilities, respectively. In facilities that performed brachytherapy, the main reason why brachytherapy of the esophagus was not performed was high invasiveness (30.2%). Definitive-dose chemoradiotherapy with (≥50 Gy) tended to be used in patients with expected long-term survival. CONCLUSIONS Few facilities routinely considered brachytherapy for the treatment of dysphagia from esophageal cancer in Japan. Conversely, most facilities routinely considered external beam radiotherapy. In the future, it will be necessary to optimize external beam radiotherapy.
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Affiliation(s)
- Terufumi Kawamoto
- Department of Radiation Oncology, Juntendo University Hospital, Tokyo, Japan
| | - Naoki Nakamura
- Department of Radiation Oncology, St. Marianna University School of Medicine Hospital, Kawasaki, Japan
| | - Tetsuo Saito
- Department of Radiation Oncology, Arao Municipal Hospital, Kumamoto, Japan
| | - Ayako Tonari
- Department of Radiation Oncology, Kyorin University Hospital, Mitaka, Japan
| | - Hitoshi Wada
- Department of Radiation Oncology, Southern TOHOKU Proton Therapy Center, Fukushima, Japan
| | - Hideyuki Harada
- Division of Radiation Therapy, Radiation and Proton Therapy Center, Shizuoka Cancer Center Hospital, Shizuoka, Japan
| | - Hikaru Kubota
- Department of Radiation Oncology, Kobe University Hospital, Kobe, Japan
| | | | - Joichi Heianna
- Department of Radiation Oncology, Ryukyu University Hospital, Nishihara, Japan
| | | | - Kazunari Yamada
- Department of Radiation Oncology, Seirei Mikatahara General Hospital, Hamamatsu, Japan
| | - Masao Tago
- Department of Radiology, Teikyo University Hospital, Tokyo, Japan
| | - Masato Fushiki
- Department of Radiation Oncology, Nagahama City Hospital, Nagahama, Japan
| | - Miwako Nozaki
- Department of Radiation Oncology, Dokkyo Medical University Saitama Medical Center, Saitama, Japan
| | - Nobue Uchida
- Department of Radiation Oncology, Tokyo Saiseikai Central Hospital, Tokyo, Japan
| | - Norio Araki
- Department of Radiation Oncology, Kyoto Medical Center, Kyoto, Japan
| | - Shuhei Sekii
- Department of Radiation Oncology, Kita-Harima Medical Center, Ono, Japan
| | - Takashi Kosugi
- Department of Radiation Oncology, Fujieda Municipal General Hospital, Fujieda, Japan
| | - Takeo Takahashi
- Department of Radiation Oncology, Saitama Medical Center, Saitama Medical University, Saitama, Japan
| | - Naoto Shikama
- Department of Radiation Oncology, Juntendo University Hospital, Tokyo, Japan
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Marguet S, Adenis A, Delaine-Clisant S, Penel N, Bonastre J. Cost-Utility Analysis of Continuation Versus Discontinuation of First-Line Chemotherapy in Patients With Metastatic Squamous-Cell Esophageal Cancer: Economic Evaluation Alongside the E-DIS Trial. VALUE IN HEALTH : THE JOURNAL OF THE INTERNATIONAL SOCIETY FOR PHARMACOECONOMICS AND OUTCOMES RESEARCH 2021; 24:676-682. [PMID: 33933236 DOI: 10.1016/j.jval.2020.11.017] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/07/2019] [Revised: 10/21/2020] [Accepted: 11/25/2020] [Indexed: 06/12/2023]
Abstract
OBJECTIVES Continuous chemotherapy has been used to treat patients with metastatic esophageal squamous cell carcinoma (mESCC), despite weak evidence supporting a clinical benefit, associated side effects for the patients, and unjustified medical costs. In the French setting, we conducted a cost-utility analysis alongside the randomized E-DIS trial (NCT01248299), which compared first-line fluorouracil/platinum-based chemotherapy continuation (CT-CONT) to CT discontinuation (CT-DISC) in progressive-free patients after an initial 6-week treatment phase. METHODS A partitioned survival analysis was performed using patient-level data collected during the trial for survival outcomes, quality of life (EQ-5D-3L), and medical costs. The mean quality-adjusted life-years (QALYs) and medical costs were estimated over an 18-month period to assess the incremental net monetary benefit and incremental cost-effectiveness ratio. Uncertainty was handled using the nonparametric bootstrap and univariate analysis. Sixty-seven patients with mESCC were randomized and included in the cost-utility analysis. RESULTS On average, CT-CONT slightly decreased the number of QALYs (-0.038) and increased the cost per patient (+ €1177). At a willingness-to-pay threshold of €50 000/QALY, the incremental net monetary benefit was negative (-€3077 [95% confidence interval: -6564; 4359]), and the incremental cost-effectiveness ratio was -30 958€/QALY (CT-CONT dominated). The probability of the CT-CONT treatment option being cost-effective at a willingness-to-pay threshold of €50 000/QALY, compared to CT-DISC, was 29%. CONCLUSIONS CT-DISC may be considered as an alternative therapeutic option to CT-CONT in patients with mESCC who have stable disease after an initial chemotherapy treatment phase. A continuous chemotherapy could indeed reduce the number of QALYs because of the disutility associated with the continuous treatment.
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Affiliation(s)
- Sophie Marguet
- Gustave Roussy, Université Paris-Saclay, Service de Biostatistique et d'Epidémiologie, Villejuif, France; Université Paris-Saclay, Paris-Sud University, Villejuif, France
| | - Antoine Adenis
- Department of Medical Oncology, Centre Oscar Lambret, Lille, France
| | | | - Nicolas Penel
- Department of Medical Oncology, Centre Oscar Lambret, Lille, France; Direction de la Recherche Clinique et de l'Innovation, Centre Oscar Lambret, Lille, France; Lille University Hospital, Lille, France
| | - Julia Bonastre
- Gustave Roussy, Université Paris-Saclay, Service de Biostatistique et d'Epidémiologie, Villejuif, France; Université Paris-Saclay, Paris-Sud University, Villejuif, France.
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Zhang L, Song Y, Jiang N, Huang Y, Dong B, Li W, He Y, Chen Y, Liu H, Yu R. Efficacy and safety of anti-epidermal growth factor receptor agents for the treatment of oesophageal cancer: a systematic review and meta-analysis. BMJ Open 2021; 11:e046352. [PMID: 33753446 PMCID: PMC7986677 DOI: 10.1136/bmjopen-2020-046352] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
OBJECTIVES Despite remarkable advances in the treatment of oesophageal cancer (OC), the role of antiepidermal growth factor receptor (anti-EGFR) agents in treating OC remains controversial. Herein, a systematic review and meta-analysis were conducted to elucidate the efficacy and safety of anti-EGFR agents in patients with OC. DESIGN Meta-analysis of randomised controlled trials (RCTs) identified by searching the PubMed, Embase, Web of Science, ClinicalTrials.gov, Cochrane Library, Chinese Biology Medicine, China National Knowledge Infrastructure and Wanfang Data Knowledge Service Platform databases from inception to December 2019. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. SETTING RCTs from any country and healthcare setting. PARTICIPANTS Patients with OC. INTERVENTIONS Combination therapy with anti-EGFR agents and conventional treatments versus conventional treatments alone in patients with OC. PRIMARY AND SECONDARY OUTCOME MEASURES Overall survival (OS) and progression-free survival (PFS) were primary outcome measures, and objective response rate (ORR), disease control rate (DCR) and treatment toxicities were secondary outcome measures. RESULTS In total, 25 RCTs comprising 3406 patients with OC were included. Overall, anti-EGFR treatment significantly improved the OS (HR: 0.81, 95% CI 0.74 to 0.89, p<0.00001), ORR (relative risk (RR): 1.33, 95% CI 1.16 to 1.52, p<0.0001) and DCR (RR: 1.22, 95% CI 1.11 to 1.34, p<0.0001) but not PFS (HR: 0.91, 95% CI 0.76 to 1.08, p=0.26). Anti-EGFR treatment was significantly associated with higher incidences of myelosuppression, diarrhoea, acne-like rash and hypomagnesaemia. CONCLUSIONS Overall, anti-EGFR agents have positive effects on OS, the ORR and DCR in OC. However, considering the high incidence of adverse effects, such as myelosuppression, diarrhoea, acne-like rashes and hypomagnesaemia, careful monitoring of patients with OC is recommended during anti-EGFR treatment. TRIAL REGISTRATION NUMBER CRD42020169230.
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Affiliation(s)
- Lijuan Zhang
- School of Nursing, Liaoning University of Traditional Chinese Medicine, Shenyang, China
| | - Yanli Song
- School of Nursing, Liaoning University of Traditional Chinese Medicine, Shenyang, China
| | - Nan Jiang
- School of Nursing, Tianjin Medical University, Tianjin, China
| | - Yaqi Huang
- School of Nursing, Tianjin Medical University, Tianjin, China
| | - Bo Dong
- School of Nursing, Liaoning University of Traditional Chinese Medicine, Shenyang, China
| | - Wei Li
- School of Nursing, Liaoning University of Traditional Chinese Medicine, Shenyang, China
| | - Yanze He
- School of Nursing, Liaoning University of Traditional Chinese Medicine, Shenyang, China
| | - Yun Chen
- Department of Colorectal Surgery, Liaoning Cancer Institute and Hospital, Shenyang, China
| | - Haibin Liu
- Department of Critical Care Medicine, Liaoning Cancer Institute and Hospital, Shenyang, China
| | - Rui Yu
- Department of Science and Technology, Liaoning University of Traditional Chinese Medicine, Shenyang, China
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Abstract
With more understanding of the tumor biology, esophageal squamous cell carcinoma (ESCC) and adenocarcinoma are increasingly recognized as different disease entities and are managed with different treatment approaches. Most patients with ESCC need systemic treatment at some point of their disease course, but only until recently, the progress in systemic treatment has been relatively stagnant compared with its adenocarcinoma counterpart. Platinum-based regimens remain the standard of care, while taxanes have been increasingly used upfront and in later lines of treatment. The attempts to personalize treatment for ESCC with various target therapies have been futile. Immune checkpoint inhibitors are now coming into play with promising activity and potentials to combine with different treatment modalities. The current chapter overviews the systemic treatment for ESCC and highlights the recent development.
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Mao C, Zeng X, Zhang C, Yang Y, Xiao X, Luan S, Zhang Y, Yuan Y. Mechanisms of Pharmaceutical Therapy and Drug Resistance in Esophageal Cancer. Front Cell Dev Biol 2021; 9:612451. [PMID: 33644048 PMCID: PMC7905099 DOI: 10.3389/fcell.2021.612451] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Accepted: 01/04/2021] [Indexed: 02/05/2023] Open
Abstract
Pharmaceutical therapies are essential for esophageal cancer (EC). For the advanced EC, the neoadjuvant therapy regimen, including chemotherapy plus radiotherapy and/or immunotherapy, is effective to achieve clinical benefit, even pathological complete response. For the unresectable, recurrent, and metastatic EC, the pharmaceutical therapy is the limited effective regimen to alleviate the disease and prolong the progression-free survival and overall survival. In this review, we focus on the pharmaceutical applications in EC treatment including cytotoxic agents, molecular targeted antibodies, and immune checkpoint inhibitors (ICIs). The chemotherapy regimen is based on cytotoxic agents such as platinum-based complexes, fluorinated pyrimidines and taxenes. Although the cytotoxic agents have been developed in past decades, the standard chemotherapy regimen is still the cisplatin and 5-FU or paclitaxel because the derived drugs have no significant advantages of overcoming the shortcomings of side effects and drug resistance. The targeted molecular therapy is an essential supplement for chemotherapy; however, there are only a few targeted therapies available in clinical practice. Trastuzumab and ramucirumab are the only two molecular therapy drugs which are approved by the US Food and Drug Administration to treat advanced and/or metastatic EC. Although the targeted therapy usually achieves effective benefits in the early stage therapy of EC, the patients will always develop drug resistance during treatment. ICIs have had a significant impact on routine clinical practice in cancer treatment. The anti-programmed cell death-1 monoclonal antibodies pembrolizumab and nivolumab, as the ICIs, are recommended for advanced EC by several clinical trials. However, the significant issues of pharmaceutical treatment are still the dose-limiting side effects and primary or secondary drug resistance. These defects of pharmaceutical therapy restrain the clinical application and diminish the effectiveness of treatment.
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Affiliation(s)
- Chengyi Mao
- Department of Thoracic Surgery West China Hospital, Sichuan University, Chengdu, China
| | - Xiaoxi Zeng
- West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, China
| | - Chao Zhang
- West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, China
| | - Yushang Yang
- Department of Thoracic Surgery West China Hospital, Sichuan University, Chengdu, China
| | - Xin Xiao
- Department of Thoracic Surgery West China Hospital, Sichuan University, Chengdu, China
| | - Siyuan Luan
- Department of Thoracic Surgery West China Hospital, Sichuan University, Chengdu, China
| | - Yonggang Zhang
- Department of Periodical Press, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China
- Nursing Key Laboratory of Sichuan Province, Chengdu, China
- Chinese Evidence-Based Medicine Center, West China Hospital, Sichuan University, Chengdu, China
| | - Yong Yuan
- Department of Thoracic Surgery West China Hospital, Sichuan University, Chengdu, China
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Attia H, Smyth E. Evolving therapies in advanced oesophago-gastric cancers and the increasing role of immunotherapy. Expert Rev Anticancer Ther 2021; 21:535-546. [PMID: 33349073 DOI: 10.1080/14737140.2021.1866548] [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] [Indexed: 12/30/2022]
Abstract
INTRODUCTION Esophagogastric cancers remain a considerable health burden and among the top causes of global cancer-related deaths. Chemotherapy remains the cornerstone of treatment for patients with advanced disease. Doublet platinum/fluoropyrimidine therapy is established as first-line treatment with the option of adding a taxane in selected patients. Irinotecan, taxanes, and ramucirumab are approved as second-line treatments. Results from the trials KEYNOTE-059, ATTRACTION-2, and TAGS have established the use of immune checkpoint inhibitors and trifluridine/tipiracil as a third-line treatment. High PD-L1 expression, microsatellite instability, tumor mutational burden, and Epstein-Barr virus status may also be used to enrich for responses to immunotherapy. AREAS COVERED In this review, we discuss the outcome of recent trials in the later lines of therapy for esophagogastric cancer and place these in the context of current treatment paradigms. We also discuss the biology of esophagogastric cancers and how this might inform the development of new treatments. Finally, we comment on promising new drugs in development. EXPERT OPINION Recent advances in the treatment of chemo-refractory esophagogastric cancer add to the improving survival of patients with this disease. Further research is needed to improve patient selection to therapies and the earlier incorporation of these agents in the treatment journey.
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Affiliation(s)
- Hossameldin Attia
- Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Cambridge, UK
| | - Elizabeth Smyth
- Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Cambridge, UK
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Chu L, Chen Y, Liu Q, Liang F, Wang S, Liu Q, Yu H, Wu X, Zhang J, Deng J, Ai D, Zhu Z, Nie Y, Zhao K. A Phase II Study of Apatinib in Patients with Chemotherapy-Refractory Esophageal Squamous Cell Carcinoma (ESO-Shanghai 11). Oncologist 2021; 26:e925-e935. [PMID: 33393167 PMCID: PMC8176978 DOI: 10.1002/onco.13668] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2020] [Accepted: 12/14/2020] [Indexed: 01/10/2023] Open
Abstract
Lessons Learned
Apatinib has potential as an effective and safe second‐line or higher treatment for patients with chemotherapy‐refractory esophageal squamous cell carcinoma (ESCC). Clinical safety is of potential concern when administering apatinib to patients with uncontrolled esophageal lesions or severe invasion of trachea, bronchi, or major blood vessels. To the best of the authors' knowledge, this is the first prospective phase II study to investigate apatinib for patients with chemotherapy‐refractory ESCC. Apatinib could provide an alternative option for ESCC after first‐line or higher therapy in carefully selected patients. Background The aim of this study was to evaluate the efficacy and adverse effects of the oral vascular endothelial growth factor receptor 2 (VEGFR‐2) tyrosine kinase inhibitor apatinib in patients with chemotherapy‐refractory esophageal squamous cell carcinoma (ESCC). Methods We enrolled patients with chemotherapy‐refractory ESCC. All patients received continuous apatinib 500 mg once daily. Results Between July 2017 and August 2018, 40 patients were recruited, of whom 5 (12.5%) had uncontrolled primary tumors. Additionally, three patients with partial response (PR) and 23 with stable disease (SD) were observed for overall response rate (ORR) of 7.5% and disease control rate (DCR) of 65.0%. Median progression‐free survival (PFS) was 3.8 months (95% confidence interval [CI], 2.2–5.4); median overall survival (OS) was 5.8 months (95% CI, 3.2–8.4). Common adverse effects were fatigue (15%), hypertension (12.5%), and palmar‐plantar erythrodysesthesia syndrome (10%). Two cases of death from massive bronchopulmonary hemorrhage were observed, and esophageal fistula occurred in another two patients. Notably, both patients with esophageal fistula and one patient with massive fatal bronchopulmonary hemorrhage were individuals with uncontrolled primary tumors (3/5, 60%). Fatal bronchopulmonary hemorrhage in a second patient was associated with major blood vessel invasion. Conclusion Apatinib has potential as an effective and safe treatment for patients with chemotherapy‐refractory ESCC whose primary tumors are controlled and without severe invasion of trachea, bronchi, or major blood vessels.
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Affiliation(s)
- Li Chu
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China
| | - Yun Chen
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China
| | - Qi Liu
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China
| | - Fei Liang
- Department of Biostatistics, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
| | - Shengping Wang
- Department of Radiology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China
| | - Quan Liu
- Department of Radiology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China
| | - Hui Yu
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China
| | - Xianghua Wu
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China
| | - Junhua Zhang
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China
| | - Jiaying Deng
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China
| | - Dashan Ai
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China
| | - Zhengfei Zhu
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China
| | - Yongzhan Nie
- State Key Laboratory of Cancer Biology & Xijing Hospital of Digest Diseases, Fourth Military Medical University, Xi'an, People's Republic of China
| | - Kuaile Zhao
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China
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A Comparison of Real-World Treatment Patterns and Clinical Outcomes in Patients Receiving First-Line Therapy for Unresectable Advanced Gastric or Gastroesophageal Junction Cancer Versus Esophageal Adenocarcinomas. Adv Ther 2021; 38:707-720. [PMID: 33244736 PMCID: PMC7854438 DOI: 10.1007/s12325-020-01567-9] [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: 08/09/2020] [Accepted: 11/10/2020] [Indexed: 12/09/2022]
Abstract
Introduction Management of locally advanced, unresectable, or metastatic (adv/met) esophageal adenocarcinoma (EAC) follows clinical guidance for gastric cancer (GC) and gastroesophageal junction cancer (GEJC). However, evidence for these guidelines is based largely on patients with adv/met GC/GEJC, and generally excludes patients with EAC. It is currently unclear whether patients with adv/met GC/GEJC and adv/met EAC have similar demographics and clinical outcomes in real-world practice. Methods Adult patients diagnosed with adv/met GC/GEJC and adv/met EAC between January 1, 2011 and November 30, 2018 were identified (Flatiron Health database); patients with confirmed human epidermal growth factor receptor 2 (HER2)-positive tumors were excluded, and index was date of adv/met diagnosis. Median overall survival (OS) from start of first-line therapy until death/censoring was estimated by the Kaplan–Meier method. Multivariable analysis (Cox proportional hazards) was conducted to identify factors associated with OS. Results In total, 3052 patients were identified (adv/met GC/GEJC, n = 2083; adv/met EAC, n = 969). Patients with EAC were more likely to be male, have a history of smoking, have a higher body weight and body mass index, and were less likely to be Hispanic/Latino or Medicaid enrollees than patients with GC/GEJC. A similar proportion of patients with adv/met GC/GEJC (75%; n = 2326) and adv/met EAC (77%; n = 1573) received first-line therapy. Fluoropyrimidine plus platinum combinations were the most frequent first-line regimen in both groups (36%). Median OS was similar for patients with adv/met GC/GEJC and adv/met EAC (9.7 vs. 9.1 months, respectively; hazard ratio [95% confidence interval] 0.96 [0.87–1.06]; p = 0.4320). Conclusion Despite minor differences in baseline demographics, clinical outcomes for patients with adv/met GC/GEJC and EAC are similar. This supports the inclusion of patients with adv/met EAC in clinical trials assessing adv/med GC/GEJC.
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Maron SB, Xu J, Janjigian YY. Targeting EGFR in Esophagogastric Cancer. Front Oncol 2020; 10:553876. [PMID: 33364187 PMCID: PMC7753114 DOI: 10.3389/fonc.2020.553876] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Accepted: 11/05/2020] [Indexed: 12/24/2022] Open
Abstract
Esophagogastric cancer (EGC) remains a major cause of cancer-related mortality. Overall survival in the metastatic setting remains poor, with few molecular targeted approaches having been successfully incorporated into routine care to-date: only first line anti-HER2 therapy in ERBB2-expressing tumors, second line anti-VEGFR2 therapy with ramucirumab in unselected patients, and pembrolizumab in PD-L1 expressing or MSI-H patients. EGFR inhibitors were extensively studied in EGC, including phase III trials with cetuximab (EXPAND), panitumumab (REAL3), and gefitinib (COG). All three trials were conducted in unselected populations, and therefore, failed to demonstrate clinical benefit. Here, we review previous attempts at targeting EGFR in EGC and potential future biomarkers for targeting this pathway in patients with EGFR-amplified tumors.
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Affiliation(s)
- Steven B Maron
- Gastrointestinal Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, United States
| | - James Xu
- Computer Engineering Program, Columbia University, New York, NY, United States
| | - Yelena Y Janjigian
- Gastrointestinal Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, United States
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Imazeki H, Kato K. Development of chemotherapeutics for unresectable advanced esophageal cancer. Expert Rev Anticancer Ther 2020; 20:1083-1092. [PMID: 32820965 DOI: 10.1080/14737140.2020.1814149] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
INTRODUCTION The prognosis of unresectable advanced esophageal squamous cell carcinoma (ESCC) has gradually improved due to efforts for the development of systemic chemotherapy or concurrent chemoradiotherapy. AREAS COVERED Chemotherapeutic agents such as cytotoxic agents, molecular-targeted agents, and immune checkpoint inhibitors, sometimes used with irradiation, lead in the treatment of unresectable advanced ESCC. Here, we review the latest treatment strategies for unresectable advanced ESCC and discuss future perspectives. EXPERT OPINION Immunotherapeutic agents will be part of the treatment of unresectable advanced ESCC in the near future. However, definitive predictive biomarkers to determine good patient candidates remain unclear for immunotherapy in patients with ESCC. Further research is warranted to identify those biomarkers working individually and in combination. Moreover, genome-based therapeutics enable individualized and patient-specific treatment. The development of molecular-targeted drugs against actionable or druggable genes is in progress.
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Affiliation(s)
- Hiroshi Imazeki
- Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital , Tokyo, Japan
| | - Ken Kato
- Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital , Tokyo, Japan
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Liu Q, Zhu Z, Chen Y, Deng J, Ai D, Liu Q, Wang S, Wu S, Chen J, Zhao K. Phase 2 Study of Stereotactic Body Radiation Therapy for Patients with Oligometastatic Esophageal Squamous Cell Carcinoma. Int J Radiat Oncol Biol Phys 2020; 108:707-715. [DOI: 10.1016/j.ijrobp.2020.05.003] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2020] [Revised: 04/28/2020] [Accepted: 05/03/2020] [Indexed: 01/26/2023]
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Peng C, Cohen DJ. Advances in the pharmacotherapeutic management of esophageal squamous cell carcinoma. Expert Opin Pharmacother 2020; 22:93-107. [PMID: 33034212 DOI: 10.1080/14656566.2020.1813278] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Esophageal squamous cancer remains an important cause of mortality worldwide with two new immunotherapy drugs recently approved for metastatic disease. AREAS COVERED The authors review the epidemiology and genomics of esophageal squamous cell carcinoma. They also examine prior trials involving targeted agents under investigation as well immunotherapies that have been approved and novel combinations. EXPERT OPINION Great advances have been made in characterizing the molecular changes in esophageal carcinoma. However, relatively few drugs have shown benefit in this disease. Targeted therapies have not shown to improve survival although many of these trials did not explore potential biomarkers. Pembrolizumab and nivolumab are now approved for esophageal squamous carcinoma but much more data are needed to understand how these agents may be used in non-metastatic settings. Novel treatments are still required as overall prognosis remains poor.
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Affiliation(s)
| | - Deirdre J Cohen
- Department of Hematology and Medical Oncology, Tisch Cancer Institute, Mount Sinai Health , New York, NY, USA
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Harada K, Rogers JE, Iwatsuki M, Yamashita K, Baba H, Ajani JA. Recent advances in treating oesophageal cancer. F1000Res 2020; 9:F1000 Faculty Rev-1189. [PMID: 33042518 PMCID: PMC7531047 DOI: 10.12688/f1000research.22926.1] [Citation(s) in RCA: 80] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/17/2020] [Indexed: 12/14/2022] Open
Abstract
Esophageal cancer (EC) is an aggressive malignancy with an increasing incidence and a poor prognosis. EC is histologically divided into two major categories: adenocarcinoma (EAC) and squamous cell carcinoma (ESCC). EAC and ESCC are molecularly different and therefore treatments should reflect the respective histological subtype. Combined modality therapy is needed for localized EC. When EC is advanced (stage 4), systemic therapy is the mainstay treatment for palliation. For localized EC, several strategies are considered standard, and more trials are necessary to determine a unified and more effective approach. The management for advanced EC is slowly evolving as immunotherapy is showing some promise for ESCC, but more data from ongoing studies are anticipated. Treatment advances will be based on high-definition genomic investigation of individual tumors. Herein, we review the contemporary trends in diagnosing and treating EAC and ESCC.
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Affiliation(s)
- Kazuto Harada
- Department of Gastrointestinal Medical Oncology, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA
- Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Jane E. Rogers
- Department of Pharmacy Clinical Program, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA
| | - Masaaki Iwatsuki
- Department of Gastrointestinal Medical Oncology, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA
- Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Kohei Yamashita
- Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Hideo Baba
- Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Jaffer A. Ajani
- Department of Gastrointestinal Medical Oncology, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA
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Uprety D, Adjei AA. KRAS: From undruggable to a druggable Cancer Target. Cancer Treat Rev 2020; 89:102070. [DOI: 10.1016/j.ctrv.2020.102070] [Citation(s) in RCA: 58] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2020] [Revised: 07/04/2020] [Accepted: 07/06/2020] [Indexed: 02/07/2023]
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