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Kunitoh H, Kakizoe T. Confronting the problems we had hoped to avoid. Jpn J Clin Oncol 2024; 54:1059-1061. [PMID: 39373090 DOI: 10.1093/jjco/hyae131] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Accepted: 09/09/2024] [Indexed: 10/08/2024] Open
Affiliation(s)
- Hideo Kunitoh
- Department of Medical Oncology, Japanese Red Cross Medical Center, Tokyo, Japan
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Zuo W, Wang Z, Qian J, Ma X, Niu Z, Ou J, Mo Q, Sun J, Li X, Wang Q, Yao Y, Yu G, Li H, Chen D, Zhang H, Geng C, Qiao G, Zhao M, Zhang B, Kang X, Zhang J, Shao Z. QL1209 (pertuzumab biosimilar) versus reference pertuzumab plus trastuzumab and docetaxel in neoadjuvant treatment for HER2-positive, ER/PR-negative, early or locally advanced breast cancer: A multicenter, randomized, double-blinded, parallel-controlled, phase III equivalence trial. Br J Cancer 2024; 131:668-675. [PMID: 38906970 PMCID: PMC11333611 DOI: 10.1038/s41416-024-02751-2] [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: 02/01/2024] [Revised: 05/29/2024] [Accepted: 06/03/2024] [Indexed: 06/23/2024] Open
Abstract
BACKGROUND This randomized, parallel-controlled, double-blinded, phase III equivalence study evaluated the equivalence of a proposed pertuzumab biosimilar QL1209 to the pertuzumab (Perjeta®) each with trastuzumab and docetaxel in neoadjuvant treatment of early or locally advanced breast cancer patients with HER2-positive, ER/PR-negative. METHODS Eligible patients were randomly (1:1) assigned to receive 4 cycles of neoadjuvant QL1209 or pertuzumab each with trastuzumab and docetaxel, and adjuvant treatment. The primary endpoint was total pathologic complete response (tpCR), with equivalence margins of 0.76 to 1.32. RESULTS Among the 585 patients enrolled, 257 and 259 patients were assigned to the QL1209 and pertuzumab groups, respectively. The tpCR rates were comparable in the QL1209 (109/255, 42.75%; 90% CI 37.65 to 47.84) and pertuzumab (117/259, 45.17%; 90% CI 40.09 to 50.26) groups. The tpCR risk ratio was 0.95 (90% CI, 0.80 to 1.11), and the 90% CI fell within the predefined equivalence margin. The most common grade ≥3 treatment-related adverse event was decreased neutrophil count (10. 9% vs. 12.7%) in the QL1209 and pertuzumab groups. CONCLUSIONS QL1209 demonstrated equivalent efficacy and comparable safety profile to the reference pertuzumab in neoadjuvant treatment of HER2-positive, ER/PR-negative, early, or locally advanced breast cancer. TRIAL REGISTRATION Chinadrugtrials.org CTR20201073; ClinicalTrials.gov NCT04629846.
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Affiliation(s)
- Wenjia Zuo
- Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
| | - Zhonghua Wang
- Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
| | - Jun Qian
- Department of Surgical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, 233099, China
| | - Xiaopeng Ma
- Department of General Surgery, The First Affiliated Hospital of USTC, Division of Life Science and Medicine, University of Science and Technology of China, Hefei, 230001, China
| | - Zhaofeng Niu
- Department of Breast Disease, Yuncheng Central Hospital, Yuncheng, 044099, China
| | - Jianghua Ou
- Department of Breast Surgery, Cancer Hospital Affiliated to Xinjiang Medical University, Urumqi, 830000, China
| | - Qinguo Mo
- Department of Breast Surgery, Guangxi Medical University Cancer Hospital, Nanning, 530021, China
| | - Jing Sun
- The Fifth Department of Internal Medicine, Anyang Tumor Hospital, Anyang, 455000, China
| | - Xinzheng Li
- Department of Breast Surgery, Shanxi Cancer Hospital, Xi'an, 710061, China
| | - Qitang Wang
- Breast Medical Center, Qingdao Central Hospital, Qingdao, 266042, China
| | - Yongzhong Yao
- Department of Breast Surgery, Department of General Surgery, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, China
| | - Guohua Yu
- Department of Oncology, Weifang People's Hospital, Weifang, 261071, China
| | - Hongsheng Li
- Department of Breast Surgery, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, 511436, Guangzhou, China
| | - Dedian Chen
- The Second Department of Breast surgery, Yunnan Cancer Hospital, Kunming, 650118, China
| | - Hao Zhang
- Department of Breast Surgery, Nanyang Central Hospital, Nanyang, 473005, China
| | - Cuizhi Geng
- Breast Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, China
| | - Guangdong Qiao
- Department of Breast Surgery, Yantai Yuhuangding Hospital, Yantai, 264099, China
| | - Mengmeng Zhao
- Clinical Research Center, Qilu Pharmaceutical Co., Ltd, Jinan, 250105, China
| | - Baihui Zhang
- Clinical Research Center, Qilu Pharmaceutical Co., Ltd, Jinan, 250105, China
| | - Xiaoyan Kang
- Clinical Research Center, Qilu Pharmaceutical Co., Ltd, Jinan, 250105, China
| | - Jin Zhang
- The Third Department of Breast Cancer, Tianjin Medical University Cancer Institute & Hospital, Tianjin, 300060, China.
| | - Zhimin Shao
- Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
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Zhang QY, Cai RG, Song GH, Li CJ, Zhang BH, Kang XY, Li HP, Xu BH. QL1701 (a proposed trastuzumab biosimilar) versus reference trastuzumab plus docetaxel as first-line therapy for HER2-positive metastatic breast cancer: a multicenter, randomized, double-blinded, parallel-controlled, phase III equivalence trial. ESMO Open 2024; 9:103682. [PMID: 39241496 PMCID: PMC11406081 DOI: 10.1016/j.esmoop.2024.103682] [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: 05/15/2024] [Revised: 07/22/2024] [Accepted: 07/29/2024] [Indexed: 09/09/2024] Open
Abstract
BACKGROUND QL1701 is a proposed biosimilar to the reference trastuzumab (Herceptin®). This trial compared the efficacy and safety of QL1701 with the reference trastuzumab in first-line treatment of human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. MATERIALS AND METHODS This randomized, double-blinded, parallel-controlled, phase III equivalence trial was conducted in 73 centers in China. Eligible patients with histologically or cytologically diagnosed HER2-positive metastatic breast cancer were randomly assigned (1 : 1) to receive either QL1701 or reference trastuzumab in combination with docetaxel (every 3 weeks) for eight cycles as the first-line treatment. Then, in patients with objective responses or stable disease, the QL1701 or reference trastuzumab with or without docetaxel was maintained for totally up to 12 months if tolerated. The primary endpoint was 24-week objective response rate (ORR) assessed by an independent review committee (IRC). The equivalence margin was 0.80-1.25 with a 90% confidence interval (CI) for the ORR ratio (QL1701 to reference trastuzumab). RESULTS Between 29 April 2020 and 15 March 2022, 474 patients were randomized, and 473 received either QL1701 (n = 236) or reference trastuzumab (n = 237). The risk ratio for 24-week ORR was 1.07 (90% CI 0.94-1.21). The 90% CI fell within the pre-specified equivalence margin of 0.80-1.25. The 24-week ORR assessed by IRC was 59.7% (95% CI 53.2% to 66.1%) versus 56.1% (95% CI 49.5% to 62.5%) in QL1701 and the reference trastuzumab, respectively. As of 12 April 2023, there were no notable differences in progression-free survival (median: 8.3 versus 8.4 months) and overall survival (1-year rate: 95.1% versus 93.3%) between the two groups. Safety, pharmacokinetic (PK), and immunogenicity profiles were similar between the two groups. CONCLUSION QL1701 demonstrated equivalent efficacy and similar safety to the reference trastuzumab when combined with docetaxel in the first-line treatment of patients with HER2-positive metastatic breast cancer, with similar PK and immunogenicity profiles.
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Affiliation(s)
- Q-Y Zhang
- Breast Cancer Ward 1, Harbin Medical University Cancer Hospital, Harbin
| | - R-G Cai
- National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing
| | - G-H Song
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Breast Oncology, Peking University Cancer Hospital and Institute, Beijing
| | - C-J Li
- Clinical Research and Development Center, Qilu Pharmaceutical Co., Ltd., Jinan, China
| | - B-H Zhang
- Clinical Research and Development Center, Qilu Pharmaceutical Co., Ltd., Jinan, China
| | - X-Y Kang
- Clinical Research and Development Center, Qilu Pharmaceutical Co., Ltd., Jinan, China
| | - H-P Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Breast Oncology, Peking University Cancer Hospital and Institute, Beijing.
| | - B-H Xu
- National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing.
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Chen M, Zhang H, He X, Lin Y. Cost-effectiveness of utidelone and capecitabine versus monotherapy in anthracycline- and taxane-refractory metastatic breast cancer. Front Pharmacol 2024; 15:1303808. [PMID: 39055495 PMCID: PMC11269192 DOI: 10.3389/fphar.2024.1303808] [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: 09/28/2023] [Accepted: 06/21/2024] [Indexed: 07/27/2024] Open
Abstract
Background This study aimed to assess the cost-effectiveness of combining utidelone with capecitabine, compared to capecitabine monotherapy, for the treatment of anthracycline- and taxane-refractory metastatic breast cancer within the Chinese healthcare system. Methods A partitioned survival model was formulated based on patient characteristics from the NCT02253459 trial. Efficacy, safety, and health economics data were sourced from the trial and real-world clinical practices. We derived estimates for costs, quality-adjusted life years (QALYs), and the incremental cost-effectiveness ratio (ICER) for the two treatment strategies. Sensitivity and subgroup analyses were conducted to rigorously evaluate uncertainties' impact. Results Over a 5-year span, the combination therapy manifested substantially higher costs than capecitabine monotherapy, with a differential of US$ 26,370.63. This combined approach conferred an additional 0.49 QALYs, resulting in an ICER of US$ 53,874.17/QALY. Utilizing the established willingness-to-pay threshold, the combination might not consistently be deemed cost-effective when juxtaposed against monotherapy. However, at an ICER of US$ 53,874.4/QALY, the probability of the combination being cost-effective increased to 48.97%. Subgroup analysis revealed that the combination was more cost-effective than capecitabine alone in specific patient groups, including those <60 years, patients with more than two chemotherapy rounds, patients lacking certain metastases, patients having limited metastatic sites, patients with an Eastern Cooperative Oncology Group status of 0, and patients with particular hormone receptor profiles. Conclusion Although the combination of utidelone and capecitabine may not be an economically viable universal choice for anthracycline- and taxane-refractory metastatic breast cancer, it could be more cost-effective in specific patient subgroups than capecitabine monotherapy.
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Affiliation(s)
- Mulan Chen
- Department of Medical Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China
| | - Heng Zhang
- Clinical Medical Research Center, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China
| | - Xiaoyan He
- Department of Endocrinology, Fuqing City Hospital of Fujian, Fuqing City Hospital Affiliated to Fujian Medical University, Fuqing, China
| | - Yingtao Lin
- Clinical Medical Research Center, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China
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Banerjee S. Cost-Effectiveness and the Economics of Genomic Testing and Molecularly Matched Therapies. Surg Oncol Clin N Am 2024; 33:231-242. [PMID: 38401907 DOI: 10.1016/j.soc.2023.12.010] [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] [Indexed: 02/26/2024]
Abstract
Cost-effectiveness analysis of precision oncology can help guide value-driven care. Next-generation sequencing is increasingly cost-efficient over single gene testing because diagnostic algorithms require multiple individual gene tests to determine biomarker status. Matched targeted therapy is often not cost-effective due to the high cost associated with drug treatment. However, genomic profiling can promote cost-effective care by identifying patients who are unlikely to benefit from therapy. Additional applications of genomic profiling such as universal testing for hereditary cancer syndromes and germline testing in patients with cancer may represent cost-effective approaches compared with traditional history-based diagnostic methods.
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Affiliation(s)
- Sudeep Banerjee
- Division of Colorectal Surgery, Department of General Surgery, Kaiser Permanente San Jose Medical Center, Kaiser Permanente Northern California, 280 Hospital Parkway, Building B, San Jose, CA 95119, USA.
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Lin YT, Wang C, He XY, Yao QM, Chen J. Comparative cost-effectiveness of first-line pembrolizumab plus chemotherapy vs. chemotherapy alone in persistent, recurrent, or metastatic cervical cancer. Front Immunol 2024; 14:1345942. [PMID: 38274823 PMCID: PMC10808689 DOI: 10.3389/fimmu.2023.1345942] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2023] [Accepted: 12/27/2023] [Indexed: 01/27/2024] Open
Abstract
Background Treating persistent, recurrent, or metastatic cervical cancer remains challenging. Although pembrolizumab, combined with chemotherapy and bevacizumab, offers a promising first-line option, its cost-effectiveness within the Chinese healthcare system has not been established. Methods A partitioned survival model was constructed using patient data from the KEYNOTE-826 trial. Efficacy, safety, and economic data from both trial and real-world practices were utilized to determine the costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER) of the treatment strategies. Comprehensive insights were gained through the sensitivity and subgroup analyses. Results Over five years, the combination of pembrolizumab, chemotherapy, and bevacizumab offered an additional 1.18 QALYs compared to that provided by standard treatments. This regimen increased the costs by US$ 134,502.57, resulting in an ICER of US$ 114,275.67 per QALY, relative to traditional treatment costs. The ICER for the pembrolizumab regimen was further calibrated to be US$ 52,765.69 per QALY. Both ICER values surpassed China's established willingness-to-pay threshold. Importantly, subgroup analysis revealed enhanced cost-effectiveness in patients presenting with a programmed death-ligand 1 combined positive score (PD-L1 CPS) ≥10. Conclusion Introducing pembrolizumab alongside chemotherapy and bevacizumab may not be a cost-effective primary strategy for advanced cervical cancer against current standards. However, for patients with a PD-L1 CPS ≥10, the therapeutic and economic outcomes could be improved by adjusting the pembrolizumab price.
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Affiliation(s)
- Ying-tao Lin
- Clinical Medical Research Center, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian, China
- Department of Drug Clinical Trial Institution, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian, China
| | - Chang Wang
- Department of Lymphoma & Head and Neck Tumors, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian, China
| | - Xiao-yan He
- Department of Endocrinology, Fuqing City Hospital of Fujian, Fuqing City Hospital Affiliated to Fujian Medical University, Fuqing, Fujian, China
| | - Qi-min Yao
- College of Finance, Fujian Jiangxia University, Fuzhou, Fujian, China
| | - Jian Chen
- Department of Gynecological-Surgical Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian, China
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Šlegerová L, Kopečková K. The Cost-Effectiveness of Pertuzumab for the Treatment of Metastatic HER2+ Breast Cancer in Czechia: A Semi-Markov Model Using Cost States. Value Health Reg Issues 2023; 38:118-125. [PMID: 37865065 DOI: 10.1016/j.vhri.2023.08.002] [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: 05/23/2022] [Revised: 07/28/2023] [Accepted: 08/02/2023] [Indexed: 10/23/2023]
Abstract
OBJECTIVES This article estimates the cost-effectiveness of adding pertuzumab to the combination of trastuzumab and docetaxel within the first-line treatment for metastatic breast cancer with the amplification of HER2+. METHODS Data from Czech clinical practice recorded in the BREAST register are used. A semi-Markov model with states derived based on the treatment phases (first-line medication, no medication, next-line medication, death) is defined to estimate costs from the healthcare payers' perspective. The benefits are estimated as patient survival until death. The Kaplan-Meier estimates are supplemented by the Cox proportional hazard and the accelerated failure time models to control for patient characteristics. Health-related quality-of-life indicators are derived from relevant literature. RESULTS Based on the used data, adding pertuzumab does not result in statistically significantly longer survival while inducing higher treatment costs (€163 360 compared with €90 112 per patient in 2018 prices). Statistically longer survival was not supported by the log-rank test (P = .97), the Cox proportional hazard model, or the accelerated failure time model using the Gompertz distribution. The incremental cost-effectiveness ratio (€87 200) substantially exceeds the willingness to pay for 1 quality-adjusted life-year (€46 500). CONCLUSIONS This analysis indicates that adding pertuzumab cannot be considered cost-effective in Czechia. However, the observed phenomenon may be attributed to the limited duration of patient follow-up periods at the time of the study's execution (mean of 20-21 months). Importantly, we find that using states connected to specific treatment phases is appropriate for a retrospective analysis of patient-level clinical data.
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Affiliation(s)
- Lenka Šlegerová
- Institute of Economic Studies, Faculty of Social Sciences, Charles University, Prague, Czechia.
| | - Kateřina Kopečková
- Department of Oncology of the Second Faculty of Medicine of Charles University and University Hospital in Motol, Prague, Czechia
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Peng Y, Wang L, Peng L, Liu Q, Yi L, Luo X, Li S, Qin S, Wan X, Tan C, Chen G. Cost-effectiveness of Trastuzumab Deruxtecan for HER2-low Advanced Breast Cancer in the United States. Clin Ther 2023; 45:965-972. [PMID: 37537015 DOI: 10.1016/j.clinthera.2023.07.014] [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: 03/07/2023] [Revised: 06/06/2023] [Accepted: 07/19/2023] [Indexed: 08/05/2023]
Abstract
PURPOSE Trastuzumab deruxtecan has been shown to be effective for advanced breast cancer with low levels of human epidermal growth factor receptor 2. To optimize the allocation of limited health care resources, this study evaluated the cost-effectiveness of trastuzumab deruxtecan from the US payer perspective. METHODS A partitioned survival model was developed to project the disease course of advanced breast cancer. Clinical efficacy, treatment utilization, safety, and cost data were gathered from the DESTINY-Breast04 (Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer) trial and the Centers for Medicare & Medicaid Services. Transition probabilities were obtained from the reported survival probabilities per DESTINY-Breast04 group. The incremental cost-effectiveness ratio (ICER), the incremental monetary benefit, and the incremental net health benefit were measured. One-way sensitivity analysis, probabilistic sensitivity analysis, and subgroup analysis were performed to explore the uncertainty of the model. FINDINGS Trastuzumab deruxtecan had an ICER of $307,751 per quality-adjusted life-year (QALY) gained, with an incremental net health benefit of -0.317 QALY and an incremental monetary benefit of -$63,313 compared with the physician's choice of alternative chemotherapy agents. Subgroup analysis indicated that trastuzumab deruxtecan had an ICER of $383,776 per QALY gained for the hormone receptor-positive subgroup and an ICER of $194,424 per QALY for the hormone receptor-negative subgroup. One-way sensitivity analysis showed that the cost of trastuzumab deruxtecan had the most impact on model outcomes. The cost-effectiveness acceptability curve projected that the probability of trastuzumab deruxtecan being cost-effective was 5% in the overall population, 2% in the hormone receptor-positive subgroup, and 56% in the hormone receptor-negative subgroup at the willingness-to-pay threshold of $200,000 per QALY. IMPLICATIONS Trastuzumab deruxtecan may be a cost-effective option for hormone receptor-negative patients with advanced breast cancer with low levels of human epidermal growth factor receptor 2.
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Affiliation(s)
- Ye Peng
- Department of Pharmacy, the Second Xiangya Hospital of Central South University, Changsha, China; Institute of Clinical Pharmacy, Central South University, Changsha, China
| | - Liting Wang
- Department of Pharmacy, the Second Xiangya Hospital of Central South University, Changsha, China; Institute of Clinical Pharmacy, Central South University, Changsha, China
| | - Liubao Peng
- Department of Pharmacy, the Second Xiangya Hospital of Central South University, Changsha, China; Institute of Clinical Pharmacy, Central South University, Changsha, China
| | - Qiao Liu
- Department of Pharmacy, the Second Xiangya Hospital of Central South University, Changsha, China
| | - Lidan Yi
- Department of Pharmacy, the Second Xiangya Hospital of Central South University, Changsha, China
| | - Xia Luo
- Department of Pharmacy, the Second Xiangya Hospital of Central South University, Changsha, China
| | - Sini Li
- The Nethersole School of Nursing, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Shuxia Qin
- Department of Pharmacy, the Second Xiangya Hospital of Central South University, Changsha, China; Institute of Clinical Pharmacy, Central South University, Changsha, China
| | - Xiaomin Wan
- Department of Pharmacy, the Second Xiangya Hospital of Central South University, Changsha, China; Institute of Clinical Pharmacy, Central South University, Changsha, China
| | - Chongqing Tan
- Department of Pharmacy, the Second Xiangya Hospital of Central South University, Changsha, China; Institute of Clinical Pharmacy, Central South University, Changsha, China
| | - Guochun Chen
- Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, China; Hunan Key Laboratory of Kidney Disease and Blood Purification, the Second Xiangya Hospital of Central South University, Changsha, China; Clinical Immunology Research Center of Central South University, Changsha, China.
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Xie J, Li S, Li Y, Li J. Cost-effectiveness of sacituzumab govitecan versus chemotherapy in patients with relapsed or refractory metastatic triple-negative breast cancer. BMC Health Serv Res 2023; 23:706. [PMID: 37386633 DOI: 10.1186/s12913-023-09728-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Accepted: 06/21/2023] [Indexed: 07/01/2023] Open
Abstract
BACKGROUND The effectiveness of sacituzumab govitecan for metastatic triple-negative breast cancer (TNBC) has been reported in recent research, however, the value of the effectiveness and cost of sacituzumab govitecan is still unclear. METHODS A microsimulation model was developed using data from the ASCENT trial to assess the cost-effectiveness of sacituzumab govitecan for patients with relapsed or refractory metastatic TNBC over a lifetime. Model inputs, including clinical data, patient characteristics, and direct medical costs, were based on the ASCENT trial, public databases, and published literature. The primary outcomes of the model were the incremental cost-effectiveness ratio (ICER) and quality-adjusted life-years (QALYs). Univariate and probabilistic sensitivity analysis (PSA) and multiple scenario analyses were performed to address the uncertainty of the model. RESULTS Our results revealed that sacituzumab govitecan versus chemotherapy costs $293,037 and yielded an additional 0.2340 of QALYs in the whole population with metastatic TNBC, leading to an ICER of $1,252,295 gained. And in the population with metastatic TNBC without brain metastasis, the sacituzumab govitecan versus chemotherapy costs $309,949 and obtained an extra 0.2633 of QALYs, which resulted in an ICER of $1,177,171/QALYs. Univariate analyses indicated that the model outcomes were most sensitive to the drug cost of sacituzumab govitecan, the utility of progression-free disease, and the utility of progressed disease. CONCLUSION From the US payer perspective, sacituzumab govitecan is unlikely to be a cost-effective option for patients with relapsed or refractory metastatic TNBC compared with chemotherapy. Based on the value standpoint, a price decrease of sacituzumab govitecan is expected to increase the cost-effectiveness of sacituzumab govitecan in patients with metastatic TNBC.
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Affiliation(s)
- Jiao Xie
- Department of Otolaryngology-Head and Neck Surgery, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China
- Clinical Nursing Teaching and Research Section, The Second Xiangya Hospital, Central South University, Changsha, 410011, China
| | - SiNi Li
- Clinical Nursing Teaching and Research Section, The Second Xiangya Hospital, Central South University, Changsha, 410011, China.
- The Nethersole School of Nursing, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong.
- Present Address: The Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan, China.
| | - YaMin Li
- Clinical Nursing Teaching and Research Section, The Second Xiangya Hospital, Central South University, Changsha, 410011, China
| | - JianHe Li
- Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, 410011, China
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Schwarz F, Arefian H, Hartmann M, Runnebaum I. Cost-effectiveness of talazoparib for patients with locally advanced or metastasized breast cancer in Germany. PLoS One 2022; 17:e0278460. [PMID: 36454738 PMCID: PMC9714746 DOI: 10.1371/journal.pone.0278460] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2021] [Accepted: 11/16/2022] [Indexed: 12/03/2022] Open
Abstract
This study evaluated factors that influence the cost-effectiveness of talazoparib, particularly for patients with a germline breast-cancer-gene-(brca)-mutation and locally advanced or metastasized breast cancer within the context of the German healthcare system. We constructed a partitioned survival model to compare medical costs and treatment effectiveness for patients with such cancers over 45 months. Transition probabilities were derived from survival data from a randomized Phase-III EMBRACA trial, utilities based on published reports, and costs in Euros, which included costs for drug acquisition, clinical monitoring, and treatment of adverse events. Willingness-to-pay thresholds were set to be multiples of the current German per capita gross domestic product. Treatment with talazoparib led to a gain of 0.32 life-years (0.22 quality-adjusted life-years). The mean total cost of €84,003 for talazoparib and €12,741 for standard therapy resulted in an incremental cost-effectiveness ratio of €223,246 per life-year and €323,932 per quality-adjusted life-year gained, indicating that talazoparib is unlikely to be cost-effective at current pricing.
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Affiliation(s)
| | | | - Michael Hartmann
- Hospital Pharmacy, Jena University Hospital, Jena, Germany
- Cancer Center Central Germany, Berlin, Germany
| | - Ingo Runnebaum
- Cancer Center Central Germany, Berlin, Germany
- Clinic for Gynecology and Reproductive Medicine, Jena University Hospital, Jena, Germany
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Leung JH, Tai YS, Wang SY, Yip Fion HT, Tsung-Chin H, Chan AL. Cost-effectiveness of trastuzumab biosimilar combination therapy and drug wastage as first-line treatment for HER2-positive metastatic breast cancer. Breast 2022; 65:91-97. [PMID: 35870421 PMCID: PMC9305615 DOI: 10.1016/j.breast.2022.07.007] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Revised: 07/02/2022] [Accepted: 07/11/2022] [Indexed: 12/01/2022] Open
Abstract
BACKGROUND The rising cost of cancer drug therapy threatens the long-term sustainability of Taiwan National Health Insurance. Cost savings can be achieved through various strategies, e.g., using smaller vial sizes, sharing vials, weight-based dosing, or switching to biosimilars. Here we aimed to examine the cost-effectiveness of a trastuzumab biosimilar combined with docetaxel (TDbiol) for treatment-naïve HER2+ metastatic breast cancer (MBC), and the financial impact of drug wastage. METHODS A Markov model with three health states was developed to assess the cost-effectiveness of trastuzumab biosimilars plus docetaxel over a 40-month time horizon in patients with HER2+ MBC. Based on the literature and our expert opinion, we assumed similar efficacy between the trastuzumab biosimilar and its reference product. The primary clinical input for the biosimilar was the same as for the reference product in the Catastrophic Patient Database (HV). Health state utilities were derived from the literature, and direct medical costs were obtained from the National Health Insurance Administration (NHIA). RESULTS In the base-case scenario, the incremental cost-effectiveness ratio (ICER) was NTD 811,050 per QALY gained. One-way sensitivity analyses showed that the model was sensitive to utilities and transition probabilities, but not particularly sensitive to the wastage assumption. In scenario analyses, the ICER was higher when applying the price for trastuzumab reference biologic (branded), than for trastuzumab biosimilar. CONCLUSION The trastuzumab biosimilar combination regimen is cost-effective and offers significant drug cost savings in Taiwan.
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Affiliation(s)
- John Hang Leung
- Department of Obstetrics and Gynecology, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan.
| | - Yun-Sheng Tai
- Department of Surgery, An-Nan Hospital, China Medical University, Tainan, Taiwan.
| | - Shyh-Yau Wang
- Department of Radiology, An-Nan Hospital, China Medical University, Tainan, Taiwan.
| | - Hei-Tung Yip Fion
- Management Office for Health Data, Clinical Trial Research Center, China Medical University Hospital, Taichung, Taiwan.
| | - Ho Tsung-Chin
- Department of Obstetrics and Gynecology, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan.
| | - Agnes Lf Chan
- Department of Pharmacy, An-Nan Hospital, China Medical University, Tainan, Taiwan.
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12
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Guevara-Cuellar CA, Parody-Rúa E, Rengifo-Mosquera MP, Del Mar Conde-Crespo M, Nuñez-Castro JM. Cost-Effectiveness Analysis of Pertuzumab Plus Trastuzumab and Docetaxel Compared With Trastuzumab and Docetaxel in the Adjuvant Treatment of Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer in Colombia. Value Health Reg Issues 2022; 32:109-118. [PMID: 36183606 DOI: 10.1016/j.vhri.2022.08.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2022] [Revised: 06/07/2022] [Accepted: 08/09/2022] [Indexed: 11/30/2022]
Abstract
OBJECTIVES The addition of pertuzumab to the scheme of docetaxel plus trastuzumab (TH) in patients with metastatic breast cancer with overexpression of human epidermal growth factor receptor 2 increases survival. Nevertheless, this addition could represent a high cost for the health system of a middle-income country such as Colombia. Therefore, it is necessary to evaluate the efficiency of the pertuzumab plus TH (PTH) scheme in comparison with TH. METHODS A partitioned survival model-based cost-utility analysis was performed. Progression-free survival and overall survival curves for each scheme were obtained from the CLEOPATRA study. The time horizon was 30 years with a discount rate of 5% for costs and quality-adjusted life-years. Total direct costs were calculated using national tariffs. Utilities were obtained from external sources. Model uncertainty was evaluated by deterministic and probabilistic sensitivity analysis. A willingness to pay value of 5180 US dollars was used. RESULTS The discounted total average costs of TH and PTH were $24 109 and $60 846, respectively. These regimens' average life-years were 5.78 and 8.38, and their quality-adjusted life-years were 3.28 and 4.51, respectively. The incremental cost-effectiveness ratio was $29 867. One-way sensitivity analysis showed that the cost of pertuzumab was the variable that explained the uncertainty in the model. The probability that PTH is cost-effective in the probabilistic sensitivity analysis is 0.0724. CONCLUSIONS The addition of pertuzumab to the TH regimen in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer has a low probability of being cost-effective from the payer's perspective in the Colombian health system.
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13
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Li JB, Lin ZC, Wong MCS, Wang HHX, Li M, Li S. A cost-effectiveness analysis of capecitabine maintenance therapy versus routine follow-up for early-stage triple-negative breast cancer patients after standard treatment from a perspective of Chinese society. BMC Med 2022; 20:320. [PMID: 36156186 PMCID: PMC9511760 DOI: 10.1186/s12916-022-02516-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2021] [Accepted: 08/04/2022] [Indexed: 12/26/2022] Open
Abstract
BACKGROUND Capecitabine maintenance therapy is safe and efficacious for early-stage triple-negative breast cancer (TNBC) patients, but the cost-effectiveness of its long-term use has not been investigated. Here, we evaluated the cost-effectiveness of capecitabine maintenance therapy, compared with routine follow-up, in early-stage TNBC patients after standard treatment from a perspective of Chinese society. METHODS A three-state Markov model based on the data from the SYSUCC-001 trial was constructed to estimate the cost-effectiveness of capecitabine maintenance therapy in a month cycle over a period of 30-year time horizon. A 5% annual discount rate was set for all costs and benefits. One-way and probabilistic sensitivity analyses were performed to explore the model uncertainties. The main outcomes include quality-adjusted life years (QALYs), incremental cost-effectiveness ratio (ICER), and the number needed to treat (NNT) to prevent one additional event. RESULTS Compared with routine follow-up, 1-year capecitabine maintenance therapy yielded an additional 1.29 quality-adjusted life years (QALYs) at an additional cost of $3391.70, with an ICER of $2630.53 (95% CI: $1159.81-$5090.12) per QALY gained. The ICER was considerably lower than the recommended willingness-to-pay (WTP) threshold (i.e., $28,130.00 per QALY). The results were sensitive to the discount rate, drug cost, and treatment cost after relapse. Further, the NNT to prevent one additional relapse case was 29.2 (95% CI: 13.2-196.6), 16.7 (95% CI: 8.4-111.6), and 12.0 (95% CI: 5.7-82.6) at 1, 2, and 5 years, respectively. CONCLUSIONS One-year capecitabine maintenance therapy for early-stage TNBC after standard treatment, compared with routine follow-up, was found to be highly cost-effective with promising clinical benefits and acceptable increased costs. Real-world studies are warranted to validate our findings in the future.
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Affiliation(s)
- Ji-Bin Li
- Department of Clinical Research, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China. .,State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China.
| | - Zhuo-Chen Lin
- Department of Medical Records, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China
| | - Martin C S Wong
- The Jockey Club School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, People's Republic of China.,Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.,School of Public Health, The Peking University, Beijing, People's Republic of China
| | - Harry H X Wang
- School of Public Health, Sun Yat-Sen University, Guangzhou, People's Republic of China
| | - Mengmeng Li
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China.,Department of Cancer Prevention Research, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China
| | - Su Li
- Department of Clinical Research, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China.,State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China
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Predictors of long-term durable response in de novo HER2-positive metastatic breast cancer and the real-world treatment experience at two institutions. Breast Cancer Res Treat 2022; 196:215-220. [DOI: 10.1007/s10549-022-06718-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2022] [Accepted: 08/14/2022] [Indexed: 11/25/2022]
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Cost-Effectiveness of Pyrotinib Plus Capecitabine versus Lapatinib Plus Capecitabine for the Treatment of HER2-Positive Metastatic Breast Cancer in China: A Scenario Analysis of Health Insurance Coverage. Curr Oncol 2022; 29:6053-6067. [PMID: 36135045 PMCID: PMC9497482 DOI: 10.3390/curroncol29090476] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Revised: 08/20/2022] [Accepted: 08/21/2022] [Indexed: 11/16/2022] Open
Abstract
Background: The overexpression of the human epidermal growth factor receptor-2 (HER2) gene is present in 20~25% of breast cancer (BC) patients, contributing to an inferior prognosis. Recent clinical trials showed that pyrotinib has promising antitumor activities and acceptable tolerability for those patients (ClinicalTrials.gov, NCT03080805 and NCT02422199). Therefore, this study aims to assess the cost-effectiveness of pyrotinib plus capecitabine versus lapatinib plus capecitabine for patients with HER2-positive metastatic BC after prior trastuzumab. Methods: A lifetime-partitioned survival model was established to evaluate health and economic outcomes with different treatment strategies. The primary outcome was the incremental cost-effectiveness ratio (ICER). Data were derived from the published literature, clinical trials, expert opinions, and other local charges. Sensitivity analyses were performed to assess the robustness of the findings. Scenario analyses were developed to make further evaluations. Results: The pyrotinib regimen had significant advantages over the lapatinib regimen after enrolling in the National Reimbursement Drug List (NRDL), with cost savings of USD 15,599.27 and a gain of 0.53 QALYs. Meanwhile, before enrolling in NRDL, the pyrotinib regimen afforded the same QALYs at a higher incremental cost of USD 45,400.64 versus the lapatinib regimen, producing an ICER of USD 85,944.79 per QALY. Scenario analyses yielded similar results. Sensitivity analyses suggested stability in the cost-effectiveness findings. Conclusions: Compared to lapatinib plus capecitabine, the pyrotinib plus capecitabine enrolled in NRDL is a cost-effective alternative second-line treatment for patients with HER2-positive metastatic BC in China.
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Magalhães MAF, Aguiar PN, Neves MBM, Lopes GDL, del Giglio A. Cost-effectiveness analysis of Ado-trastuzumab emtansine for the treatment of residual invasive HER2-positive breast cancer. EINSTEIN-SAO PAULO 2022; 20:eGS6655. [PMID: 35544899 PMCID: PMC9071260 DOI: 10.31744/einstein_journal/2022gs6655] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2021] [Accepted: 12/22/2021] [Indexed: 12/24/2022] Open
Abstract
Objective Methods Results Conclusion
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Dai WF, Beca JM, Nagamuthu C, Liu N, de Oliveira C, Earle CC, Trudeau M, Chan KKW. Cost-effectiveness Analysis of Pertuzumab With Trastuzumab in Patients With Metastatic Breast Cancer. JAMA Oncol 2022; 8:597-606. [PMID: 35201264 PMCID: PMC8874900 DOI: 10.1001/jamaoncol.2021.8049] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2021] [Accepted: 12/08/2021] [Indexed: 12/20/2022]
Abstract
IMPORTANCE The initial assessment of pertuzumab use for treatment of metastatic breast cancer by health technology assessment agencies suggested that pertuzumab was not cost-effective. In Ontario, Canada, pertuzumab became funded in November 2013 based on the substantial clinical benefit. To date, there is a paucity of analysis of pertuzumab using real-world data for cost-effectiveness. OBJECTIVE To assess the cost-effectiveness of pertuzumab, trastuzumab, and chemotherapy vs trastuzumab and chemotherapy for patients with metastatic breast cancer. DESIGN, SETTING, AND PARTICIPANTS A population-based retrospective economic evaluation was conducted in Ontario, Canada. Patients who received first-line treatments for metastatic breast cancer from January 1, 2008, to March 31, 2018, were identified. Patients were followed up from the start of treatment up to 5 years, with maximum follow-up to March 31, 2019. Patients were identified from the Ontario Cancer Registry and linked to the New Drug Funding Program database to identify receipt of first-line treatment (N = 1158). INTERVENTIONS Treatment with pertuzumab, trastuzumab, and chemotherapy after public funding (November 25, 2013) compared with treatment with trastuzumab and chemotherapy before funding. MAIN OUTCOMES AND MEASURES Cost-effectiveness, from a public payer perspective, was estimated from administrative data with a 5-year time horizon, adjusted for censoring, and discounted (1.5%). Incremental cost-effectiveness ratios for life-years gained and quality-adjusted life year (QALY) with bootstrapped 95% CIs were calculated. Sensitivity analysis with price reduction of pertuzumab alone or in combination with trastuzumab was conducted. RESULTS A total of 579 pairs of matched patients receiving pertuzumab and controls were included. The mean (SD) age of the matched study cohort was 58 (12.97) years; 1151 were women (99.4%). Pertuzumab resulted in 0.61 life-years gained and 0.44 QALYs gained at an incremental cost of $192 139 (all costs measured in Canadian dollar values, CAD) with an incremental cost-effectiveness ratio of $316 203 per life-year gained and $436 679 per QALY. The main factors associated with cost included the cost of pertuzumab (60%), outpatient cancer treatment delivery (24%), and trastuzumab (15%). With 100% price reduction of pertuzumab, the incremental cost-effectiveness ratio was $174 027 per QALY. When the price of pertuzumab and trastuzumab were both reduced by more than 71%, the incremental cost-effectiveness ratio decreased below $100 000 per QALY. CONCLUSIONS AND RELEVANCE The findings of this population-based study suggest that pertuzumab may increase survival for patients with metastatic breast cancer but would not be considered cost-effective, even after 100% price reduction, under conventional thresholds.
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Affiliation(s)
- Wei Fang Dai
- Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
- Canadian Centre for Applied Research in Cancer Control, Toronto, Ontario, Canada
| | - Jaclyn M. Beca
- Canadian Centre for Applied Research in Cancer Control, Toronto, Ontario, Canada
- Ontario Health, Ontario, Canada
| | | | | | - Claire de Oliveira
- ICES, Ontario, Canada
- Centre for Health Economics and Hull York Medical School, University of York, York, United Kingdom
| | | | | | - Kelvin K. W. Chan
- Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
- Canadian Centre for Applied Research in Cancer Control, Toronto, Ontario, Canada
- Ontario Health, Ontario, Canada
- Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
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Hua X, Bi XW, Zhao JL, Shi YX, Lin Y, Wu ZY, Zhang YQ, Zhang LH, Zhang AQ, Huang H, Liu XM, Xu F, Guo Y, Xia W, Hong RX, Jiang KK, Xue C, An X, Zhong YY, Wang SS, Huang JJ, Yuan ZY. Trastuzumab Plus Endocrine Therapy or Chemotherapy as First-line Treatment for Patients with Hormone Receptor-Positive and HER2-Positive Metastatic Breast Cancer (SYSUCC-002). Clin Cancer Res 2022; 28:637-645. [PMID: 34810217 PMCID: PMC9377763 DOI: 10.1158/1078-0432.ccr-21-3435] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2021] [Revised: 10/29/2021] [Accepted: 11/19/2021] [Indexed: 01/07/2023]
Abstract
PURPOSE There is no research evidence demonstrate which is the better partner strategy, endocrine therapy or chemotherapy, to combine with anti-HER2 therapy as the first-line management of hormone receptor (HR)-positive (HR+) and HER2-positive (HER2+) metastatic breast cancer (MBC). We wished to ascertain if trastuzumab plus endocrine therapy is noninferior to trastuzumab plus chemotherapy. PATIENTS AND METHODS We conducted an open-label, noninferiority, phase III, randomized, controlled trial (NCT01950182) at nine hospitals in China. Participants, stratified by previous adjuvant endocrine therapy and disease status (recurrent disease vs. de novo metastasis), were assigned randomly (1:1) to receive trastuzumab plus endocrine therapy (per investigator's choice of oestrogen-receptor modulators or aromatase inhibitor, with/without concurrent ovarian suppression) or chemotherapy (per investigator's choice of taxanes, capecitabine, or vinorelbine). The primary endpoint was progression-free survival (PFS) with a noninferiority upper margin of 1.35 for the HR. The intention-to-treat population was used in primary and safety analyses. RESULTS A total of 392 patients were enrolled and assigned randomly to receive trastuzumab plus endocrine therapy (ET group, n = 196) or trastuzumab plus chemotherapy (CT group, n = 196). After a median follow-up of 30.2 months [interquartile range (IQR) 15.0-44.7], the median PFS was 19.2 months [95% confidence interval (CI), 16.7-21.7)] in the ET group and 14.8 months (12.8-16.8) in the CT group (hazard ratio, 0.88; 95% CI, 0.71-1.09; Pnoninferiority < 0.0001). A significantly higher prevalence of toxicity was observed in the CT group compared with the ET group. CONCLUSIONS Trastuzumab plus endocrine therapy was noninferior to trastuzumab plus chemotherapy in patients with HR+HER2+ MBC.
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Affiliation(s)
- Xin Hua
- Department of Medical Oncology, the State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Xi-Wen Bi
- Department of Medical Oncology, the State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Jian-Li Zhao
- Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yan-Xia Shi
- Department of Medical Oncology, the State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Ying Lin
- Thyroid and Breast Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Zhi-Yong Wu
- Department of Oncology Surgery, Diagnosis and Treatment Center of Breast Diseases, Affiliated Shantou Hospital, Sun Yat-sen University, Shantou, China
| | - Yuan-Qi Zhang
- Department of Vascular Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang, China
| | - Le-Hong Zhang
- Department of Breast Oncology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - An-Qing Zhang
- Department of Breast Oncology, Maternal and Child Health Care Hospital of Guangdong Province, Guangzhou, China
| | - Heng Huang
- Department of Breast Oncology, Lianjiang Pepole's Hospital, Lianjiang, China
| | - Xin-Mei Liu
- Department of Breast Oncology, Haikou People's Hospital, Haikou, China
| | - Fei Xu
- Department of Medical Oncology, the State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Ying Guo
- Department of Good Clinical Practice, the State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Wen Xia
- Department of Medical Oncology, the State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Ruo-Xi Hong
- Department of Medical Oncology, the State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Kui-Kui Jiang
- Department of Medical Oncology, the State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Cong Xue
- Department of Medical Oncology, the State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Xin An
- Department of Medical Oncology, the State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Yong-Yi Zhong
- Department of Medical Oncology, the State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Shu-Sen Wang
- Department of Medical Oncology, the State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Jia-Jia Huang
- Department of Medical Oncology, the State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Zhong-Yu Yuan
- Department of Medical Oncology, the State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
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Wu Q, Qin Y, Liao W, Zhang M, Yang Y, Zhang P, Li Q. Cost-effectiveness of enfortumab vedotin in previously treated advanced urothelial carcinoma. Ther Adv Med Oncol 2022; 14:17588359211068733. [PMID: 35096146 PMCID: PMC8796084 DOI: 10.1177/17588359211068733] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2021] [Accepted: 12/06/2021] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Antibody-drug conjugates have recently been introduced as a treatment for advanced urothelial carcinoma. The EV-301 study demonstrated that enfortumab vedotin (EV) improved overall survival compared with conventional chemotherapy. To assess the cost-effectiveness of EV for the treatment of advanced urothelial carcinoma (UC) from a payer perspective in middle- and high-income countries. METHODS A decision analysis model was developed to assess the efficacy and economic viability of EV as a subsequent-line treatment following disease progression in patients with advanced urothelial carcinoma already treated with PD-1 or PD-L1 inhibitors. Clinical and utility values were obtained from the published literature and available databases. Cost data were obtained from payer perspectives in the United States, United Kingdom, and China. Quality-adjusted life-years (QALYs) were used to measure health outcomes, and incremental cost-effectiveness ratios (ICERs) used to evaluate cost-effectiveness in comparison to willingness-to-pay in the United States, United Kingdom, and China. One-way sensitivity analysis and probabilistic sensitivity analysis were performed to assess the robustness of the model. RESULTS Compared with chemotherapy, EV increased the benefit by 0.16-0.17 QALYs, resulting in ICERs of $2,168,746.71, $2,164,494.38, and $1,775,576.56 per QALY in the United States, United Kingdom, and China, respectively. One-way sensitivity analysis indicated that the largest effect on outcome was the utility value for progression-free survival. Probabilistic sensitivity analysis demonstrated that the probability of EV being cost-effective was 0%. CONCLUSIONS EV provides an additional health benefit over chemotherapy for patients with advanced urothelial carcinoma but is not cost-effective from a payer perspective in the United States, United Kingdom, or China.
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Affiliation(s)
- Qiuji Wu
- Cancer Center, Department of Medical Oncology, West China Hospital, Sichuan University, Chengdu, ChinaWest China Biomedical Big Data Center, Sichuan University, Chengdu, China
| | - Yi Qin
- Cancer Center, Department of Medical Oncology, West China Hospital, Sichuan University, Chengdu, ChinaWest China Biomedical Big Data Center, Sichuan University, Chengdu, China
| | - Weiting Liao
- Cancer Center, Department of Medical Oncology, West China Hospital, Sichuan University, Chengdu, ChinaWest China Biomedical Big Data Center, Sichuan University, Chengdu, China
| | - Mengxi Zhang
- Cancer Center, Department of Medical Oncology, West China Hospital, Sichuan University, Chengdu, ChinaWest China Biomedical Big Data Center, Sichuan University, Chengdu, China
| | - Yang Yang
- Cancer Center, Department of Medical Oncology, West China Hospital, Sichuan University, Chengdu, ChinaWest China Biomedical Big Data Center, Sichuan University, Chengdu, China
| | - Pengfei Zhang
- Cancer Center, Department of Medical Oncology, West China Hospital, Sichuan University, Chengdu, ChinaWest China Biomedical Big Data Center, Sichuan University, Chengdu, China
| | - Qiu Li
- Cancer Center, Department of Medical Oncology, West China Hospital, Sichuan University, No. 37 Guo Xue Xiang, Chengdu 610041, China West China Biomedical Big Data Center, Sichuan University, Chengdu, China
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Zhou D, Wu Y, Jiang K, Xu F, Hong R, Wang S. Identification of a risk prediction model for clinical prognosis in HER2 positive breast cancer patients. Genomics 2021; 113:4088-4097. [PMID: 34666190 DOI: 10.1016/j.ygeno.2021.10.010] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2020] [Revised: 10/03/2021] [Accepted: 10/12/2021] [Indexed: 12/24/2022]
Abstract
Background New biomarkers are needed to identify different clinical outcomes for HER2+ breast cancer (BC). Methods Differential genes of HER2+ BC were screened based on TCGA database. We used WGCNA to identify the genes related to the survival. Genetic Algorithm was used to structure risk prediction model. The prognostic model was validated in GSE data. Results We constructed a risk prediction model of 6 genes to identify prognosis of HER2+ BC, including CLEC9A, PLD4, PIM1, PTK2B, AKNAD1 and C15orf27. Kaplan-Meier curve showed that the model effectively distinguished the survival of HER2+ BC patients. The multivariate Cox regression suggested that the risk model was an independent predictor for HER2+ BC. Analysis related to immune showed that significant differences in immune infiltration between high- and low-risk groups classified by the prognostic model. Conclusions Our study identified a risk prediction model of 6 genes that could distinguish the prognosis of HER2+ BC.
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Affiliation(s)
- Danyang Zhou
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.
| | - Ying Wu
- Department of Minimally Invasive Interventional Therapy, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.
| | - Kuikui Jiang
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.
| | - Fei Xu
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.
| | - Ruoxi Hong
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.
| | - Shusen Wang
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.
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Moriwaki K, Uechi S, Fujiwara T, Hagino Y, Shimozuma K. Economic Evaluation of First-Line Pertuzumab Therapy in Patients with HER2-Positive Metastatic Breast Cancer in Japan. PHARMACOECONOMICS - OPEN 2021; 5:437-447. [PMID: 33483889 PMCID: PMC8333148 DOI: 10.1007/s41669-020-00254-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 12/27/2020] [Indexed: 05/17/2023]
Abstract
OBJECTIVE The purpose of this analysis was to evaluate the cost effectiveness of the combination of pertuzumab, trastuzumab, and docetaxel (PTD) for the treatment of patients with human epidermal growth factor receptor-2 (HER2)-positive breast cancer in Japan. METHODS A partitioned survival analysis model was developed to predict costs and quality-adjusted life-years (QALYs) in a PTD arm and a trastuzumab plus docetaxel (TD) arm. Direct medical costs were considered from the perspective of the Japanese healthcare system. The time horizon of the model was set to 20 years. Data on overall survival and progression-free survival were derived from the CLEOPATRA trial. Cost parameters were estimated using a real-world claims database. Utilities were derived from published sources outside Japan. The incremental cost-effectiveness ratio (ICER) of PTD therapy compared with TD therapy was estimated. Sensitivity analysis was conducted to assess the uncertainty in parameter settings. RESULTS Compared with TD therapy, PTD therapy incurred an additional cost of $US174,479 and conferred an additional 0.949 QALYs. This resulted in an ICER of $US183,901 per QALY gained. Utility weights for progression-free survival and progressed disease had a relatively large impact on the base-case result, but the ICERs remained higher than $US75,000 per QALY over the full range of model parameters. Based on a probabilistic sensitivity analysis, the probability that PTD is cost effective was estimated to be 3.3%. CONCLUSIONS Applying a willingness-to-pay threshold of $US75,000 per QALY, PTD therapy as first-line therapy would not be cost effective. Further research is required on utilities and clinical benefits for Japanese patients with breast cancer.
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Affiliation(s)
- Kensuke Moriwaki
- Comprehensive Unit for Health Economic Evidence Review and Decision Support (CHEERS), Research Organization of Science and Technology, Ritsumeikan University, #209, Research Park Bid. No. 2, 134, Minami-machi, Chudoji, Simogyo-ku, Kyoto, 600-8813, Japan.
- Laboratory of Medical Statistics, Kobe Pharmaceutical University, 4-19-1, Motoyamakita-machi, Higashinada-ku, Hyogo, 658-8558, Japan.
| | - Saki Uechi
- Laboratory of Medical Statistics, Kobe Pharmaceutical University, 4-19-1, Motoyamakita-machi, Higashinada-ku, Hyogo, 658-8558, Japan
| | - Takaaki Fujiwara
- Laboratory of Medical Statistics, Kobe Pharmaceutical University, 4-19-1, Motoyamakita-machi, Higashinada-ku, Hyogo, 658-8558, Japan
| | - Yu Hagino
- Laboratory of Medical Statistics, Kobe Pharmaceutical University, 4-19-1, Motoyamakita-machi, Higashinada-ku, Hyogo, 658-8558, Japan
| | - Kojiro Shimozuma
- Comprehensive Unit for Health Economic Evidence Review and Decision Support (CHEERS), Research Organization of Science and Technology, Ritsumeikan University, #209, Research Park Bid. No. 2, 134, Minami-machi, Chudoji, Simogyo-ku, Kyoto, 600-8813, Japan
- Division of Health Service Research, Department of Biomedical Science, College of Life Sciences, Ritsumeikan University, 1-1-1, Noji-higashi, Kusatsu, Shiga, 525-8577, Japan
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Diaby V, Almutairi RD, Babcock A, Moussa RK, Ali A. Cost-effectiveness of treatments for HER2-positive metastatic breast cancer and associated metastases: an overview of systematic reviews. Expert Rev Pharmacoecon Outcomes Res 2021; 21:353-364. [PMID: 33213205 PMCID: PMC8765058 DOI: 10.1080/14737167.2021.1848553] [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: 08/30/2020] [Accepted: 11/06/2020] [Indexed: 12/24/2022]
Abstract
Introduction: Treatment of human epithelial growth factor receptor 2 (HER2)-positive breast cancer has rapidly evolved over the past decades with the addition of trastuzumab, lapatinib, pertuzumab, and trastuzumab emtansine (T-DM1). These treatments have dramatically impacted the survival of HER2-positive metastatic breast cancer (mBC) patients. Nonetheless, these agents are associated with high price tags, begging the question, 'Are treatments for HER2-positive metastatic breast cancer and associated metastases cost-effective'?Areas covered: We examine evidence on the cost-effectiveness of treatments for HER2-positive metastatic breast cancer and associated metastases through a review of systematic reviews on the topic. Additionally, we discuss the implications of our findings and provide recommendations for future directions in the assessment of the cost-effectiveness of targeted directed agents for HER2-positive mBC.Expert opinion: Heterogeneous evidence from cost-effectiveness studies on the use of targeted directed agents for HER2-positive mBC across the world caution against cross-country comparisons of the value of such treatments. It also militates in favor of the production and use of cost-effectiveness analyses for local rather than global decision-making, thus ensuring that economic evaluations reflect the needs of local decision-makers and populations for which they are devised.
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Affiliation(s)
- Vakaramoko Diaby
- Department of Pharmaceutical Outcomes and Policy (POP), College of Pharmacy, HPNP 3317, University of Florida, Gainesville, FL, USA
| | - Reem D. Almutairi
- Department of Pharmaceutical Business and Administration Sciences, MCPHS University, Boston, MA, USA
| | - Aram Babcock
- Department of Pharmaceutical Outcomes and Policy (POP), College of Pharmacy, HPNP 3317, University of Florida, Gainesville, FL, USA
| | - Richard K. Moussa
- Université De Cergy-Pontoise, France and Ecole Nationale Supérieure De Statistiques Et d’Economie Appliquée (ENSEA), Côte d’Ivoire
| | - Askal Ali
- College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL, USA
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Sohi GK, Levy J, Delibasic V, Davis LE, Mahar AL, Amirazodi E, Earle CC, Hallet J, Hammad A, Shah R, Mittmann N, Coburn NG. The cost of chemotherapy administration: a systematic review and meta-analysis. THE EUROPEAN JOURNAL OF HEALTH ECONOMICS : HEPAC : HEALTH ECONOMICS IN PREVENTION AND CARE 2021; 22:605-620. [PMID: 33687618 DOI: 10.1007/s10198-021-01278-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/05/2020] [Accepted: 02/25/2021] [Indexed: 06/12/2023]
Abstract
PURPOSE Cancer treatment is a significant driver of healthcare costs worldwide, however, the economic impact of treating patients with anti-neoplastic agents is poorly elucidated. We conducted a systematic review and meta-analysis to estimate the direct costs associated with administering intravenous chemotherapy in an outpatient setting. METHODS We systematically searched four databases from 2010 to present and extracted hourly administration costs and the respective components of each estimate. Separate analyses were conducted of Canadian and United States (US) studies, respectively, to address a priori hypotheses regarding heterogeneity amongst estimates. The Drummond checklist was used to assess risk-of-bias. Data were summarized using medians with interquartile ranges and five outliers were identified; costs were presented in 2019 USD. RESULTS Forty-four studies were analyzed, including sub-analyses of 19 US and seven Canadian studies. 26/44 studies were of moderate-high quality. When components of administration cost were evaluated, physician costs were reported most frequently (24 studies), followed by lab tests (13) and overhead costs (9). The median estimate (excluding outliers) was $142/hour (IQR = $103-166). The median administration cost in the US was $149/hour (IQR = $118-158), and was $128/hour (IQR = $102-137) in Canada. CONCLUSIONS There is currently a paucity of literature addressing the costs of chemotherapy administration, and existing studies utilize a patchwork of reporting methodologies which renders direct comparison challenging. Our results demonstrate that the cost of administering chemotherapy is approximately $125-150/hour, globally. This value is dependent upon the region of analysis, inclusiveness of cost subcomponents as well as the methodology used to estimate unit prices, as described here.
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Affiliation(s)
- Gursharan K Sohi
- Department of Evaluative Clinical Sciences, Sunnybrook Research Institute, Toronto, ON, Canada
| | - Jordan Levy
- Division of General Surgery, Odette Cancer Centre, Sunnybrook Health Sciences Centre, 2075 Bayview Ave., Room T2 011, Toronto, ON, M4N 3M5, Canada
| | - Victoria Delibasic
- Department of Evaluative Clinical Sciences, Sunnybrook Research Institute, Toronto, ON, Canada
| | - Laura E Davis
- Department of Evaluative Clinical Sciences, Sunnybrook Research Institute, Toronto, ON, Canada
| | - Alyson L Mahar
- Department of Community Health Sciences, University of Manitoba, Winnipeg, MB, Canada
| | - Elmira Amirazodi
- Department of Evaluative Clinical Sciences, Sunnybrook Research Institute, Toronto, ON, Canada
| | - Craig C Earle
- Division of Medical Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada
| | - Julie Hallet
- Division of General Surgery, Odette Cancer Centre, Sunnybrook Health Sciences Centre, 2075 Bayview Ave., Room T2 011, Toronto, ON, M4N 3M5, Canada
| | | | - Rajan Shah
- Department of Evaluative Clinical Sciences, Sunnybrook Research Institute, Toronto, ON, Canada
| | - Nicole Mittmann
- Division of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada
| | - Natalie G Coburn
- Division of General Surgery, Odette Cancer Centre, Sunnybrook Health Sciences Centre, 2075 Bayview Ave., Room T2 011, Toronto, ON, M4N 3M5, Canada.
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24
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Awano N, Izumo T, Inomata M, Kuse N, Tone M, Takada K, Muto Y, Fujimoto K, Kimura H, Miyamoto S, Igarashi A, Kunitoh H. Medical costs of lung cancer care in Japan during the first one or two years after initial diagnosis. Jpn J Clin Oncol 2021; 51:778-785. [PMID: 33506249 DOI: 10.1093/jjco/hyaa258] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2020] [Accepted: 12/19/2020] [Indexed: 11/13/2022] Open
Abstract
OBJECTIVES Japan's healthcare expenditures, especially on oncology, are rapidly growing; however, there are scant data on actual costs and cost-effectiveness in the real world. The aim was to assess the medical costs and outcomes of patients with advanced lung cancer. METHODS We retrospectively investigated all patients who were diagnosed with advanced lung cancer at the Japanese Red Cross Medical Center between 1 January 2008 and 31 December 2018. Patients were classified into three cohorts according to the year of diagnosis-Cohort 1: 2008-2010, Cohort 2: 2011-2014 and Cohort 3: 2015-2018-and assessed for medical costs and outcome. Medical costs were divided into outpatient and inpatient costs and were calculated on a monthly basis. RESULTS Ninety-five patients with small cell lung cancer (SCLC) and 330 with nonsmall cell lung cancer (NSCLC) were included. There was a trend toward increased costs during the first two years after diagnosis in NSCLC patients, without changes in monthly costs, reflecting improved survival. Compared to Cohort 1, Cohort 3 patients with NSCLC had longer survival (median: 24 versus 12 months, P < 0.001), with a median incremental cost of Japanese Yen 6 million during the initial two years. The proportion of outpatient costs increased over time, especially for NSCLC patients (P < 0.001). No changes in costs or survival were observed in SCLC patients. CONCLUSIONS In NSCLC patients, medical costs increased with prolonged survival during the last decade. The costs on a monthly basis did not change. The proportion of outpatient costs increased.
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Affiliation(s)
- Nobuyasu Awano
- Department of Respiratory Medicine, Japanese Red Cross Medical Center, Tokyo, Japan
| | - Takehiro Izumo
- Department of Respiratory Medicine, Japanese Red Cross Medical Center, Tokyo, Japan
| | - Minoru Inomata
- Department of Respiratory Medicine, Japanese Red Cross Medical Center, Tokyo, Japan
| | - Naoyuki Kuse
- Department of Respiratory Medicine, Japanese Red Cross Medical Center, Tokyo, Japan
| | - Mari Tone
- Department of Respiratory Medicine, Japanese Red Cross Medical Center, Tokyo, Japan
| | - Kohei Takada
- Department of Respiratory Medicine, Japanese Red Cross Medical Center, Tokyo, Japan
| | - Yutaka Muto
- Department of Respiratory Medicine, Japanese Red Cross Medical Center, Tokyo, Japan
| | - Kazushi Fujimoto
- Department of Respiratory Medicine, Japanese Red Cross Medical Center, Tokyo, Japan
| | - Hitomi Kimura
- Department of Pharmacy, Japanese Red Cross Medical Center, Tokyo, Japan
| | - Shingo Miyamoto
- Department of Medical Oncology, Japanese Red Cross Medical Center, Tokyo, Japan
| | - Ataru Igarashi
- Unit of Public Health and Preventive Medicine, Yokohama City University School of Medicine, Japan.,Department of Health Economics and Outcomes Research, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan
| | - Hideo Kunitoh
- Department of Medical Oncology, Japanese Red Cross Medical Center, Tokyo, Japan
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25
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Jiao B, Garrison LP. The challenge of value-based pricing in combination therapy: the case of trastuzumab and pertuzumab in HER2+ metastatic breast cancer. Expert Rev Pharmacoecon Outcomes Res 2021; 21:497-504. [PMID: 33645393 DOI: 10.1080/14737167.2021.1896968] [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] [Indexed: 10/22/2022]
Abstract
BACKGROUND Under current reimbursement (CR) practice even though an add-on drug in a combination therapy may produce marginal value in terms of health gain, the original therapy may also share in the reward for this additional value. We examine an alternative 'marginal value-based reimbursement' (MVBR) model in which an original therapy would not share in the marginal value. METHODS In a case study for treatment of HER2+ metastatic breast cancer, we computed the incremental cost-effectiveness ratios (ICERs) of adding pertuzumab to trastuzumab and docetaxel (PHT) vs. trastuzumab and docetaxel (HT) under the CR and the MVBR models, respectively. We further estimated the revised cost of pertuzumab under three alternative willingness-to-pay thresholds based on (a) using the current ICER of PHT vs. HT, (b) the historical ICER of HT vs. docetaxel, and (c) applying the oft-used $150,000/quality-adjusted life year (QALY) gained. RESULTS If reimbursement were changed from CR to MVBR, at the current price of pertuzumab, the ICER would decline from $409,213 to $323,236/QALY gained. If the price were adjusted under the three thresholds, the payment for pertuzumab would be increased by between 32% and 93%. CONCLUSION The proposed MVBR model would provide a stronger economic incentive to develop add-on drugs.
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Affiliation(s)
- Boshen Jiao
- The Comparative Health Outcomes, Policy, and Economics (CHOICE) Institute, School of Pharmacy, University of Washington, Seattle, WA, USA
| | - Louis P Garrison
- The Comparative Health Outcomes, Policy, and Economics (CHOICE) Institute, School of Pharmacy, University of Washington, Seattle, WA, USA
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26
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Cheng LJ, Loke L, Lim EH, Pearce F, Aziz MIA, Ng K. Cost-effectiveness of pertuzumab and trastuzumab biosimilar combination therapy as initial treatment for HER2-positive metastatic breast cancer in Singapore. Expert Rev Pharmacoecon Outcomes Res 2021; 21:449-456. [PMID: 33595372 DOI: 10.1080/14737167.2021.1880323] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
BACKGROUND This study evaluates the cost-effectiveness of pertuzumab with trastuzumab biosimilar and docetaxel as initial treatment for HER2-positive metastatic breast cancer (MBC) in Singapore. METHODS A partitioned survival model with three health states was developed to evaluate the cost-effectiveness of trastuzumab biosimilar and docetaxel with or without pertuzumab from a healthcare system perspective over a 15-year time horizon for patients with HER2-positive MBC. Key clinical inputs were derived from the CLEOPATRA trial. Health state utilities were derived from the literature and direct medical costs were obtained from local public healthcare institutions. RESULTS The base-case resulted in an incremental cost-effectiveness ratio (ICER) of SGD366,658 (USD272,244) per quality-adjusted life-year (QALY) gained. One-way sensitivity analyses showed that the ICER was sensitive to utilities in the progression-free state, price of pertuzumab and time horizon. When the price for trastuzumab reference biologic (branded) was applied, the ICER was even higher (SGD426,996 [USD317,045]/QALY). CONCLUSION Although trastuzumab biosimilar reduced the cost of the pertuzumab combination regimen, the ICER remained high and was not cost effective in Singapore's context. As pertuzumab contributed 80% of the overall combination treatment cost, price reductions for pertuzumab will be required to improve the cost-effectiveness of combination treatment to an acceptable level.
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Affiliation(s)
- Li-Jen Cheng
- Agency for Care Effectiveness (ACE), Ministry of Health, Singapore
| | - Lydia Loke
- Agency for Care Effectiveness (ACE), Ministry of Health, Singapore
| | | | - Fiona Pearce
- Agency for Care Effectiveness (ACE), Ministry of Health, Singapore
| | | | - Kwong Ng
- Agency for Care Effectiveness (ACE), Ministry of Health, Singapore
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27
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Wu Q, Liao W, Zhang M, Huang J, Zhang P, Li Q. Cost-Effectiveness of Tucatinib in Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer From the US and Chinese Perspectives. Front Oncol 2020; 10:1336. [PMID: 32850425 PMCID: PMC7417356 DOI: 10.3389/fonc.2020.01336] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2020] [Accepted: 06/26/2020] [Indexed: 02/05/2023] Open
Abstract
Background: The clinical evaluation of HER2CLIMB trial showed a 21. 9-month median overall survival with the triplet regimens of tucatinib, capecitabine, and trastuzumab (TXT) for patients with human epidermal growth factor receptor 2 (HER2) –overexpressing metastatic breast cancer. From the payer's perspective of the United States and China, a cost-effectiveness analysis was conducted to evaluate the costs and benefits of adding tucatinib in this study. Methods: We constructed a Markov model for the economic evaluation of adding tucatinib to trastuzumab plus capecitabine in patients with HER-2 positive metastatic breast cancer in the United States and China. The model was conducted with a 10-year time horizon, and the health status was divided into three states: progression-free survival, progressing disease, and death. The health utility scores were consistent with published literature with similar patient status. The transition probabilities were derived from the survival data of the HER2CLIMB study. The unit prices of medicines were obtained from the West China Hospital, Red Book, and published literature. Outcomes were measured in quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio, which robustness was evaluated by deterministic and probabilistic sensitivity analyses. Results: Compared with the two-drug regimen of trastuzumab plus capecitabine (TX), the addition of tucatinib increased 0.21 QALY, with an increasing cost of $146,995.05 and $19,022.97 in the United States and China, respectively. The incremental cost-effectiveness ratios (ICERs) for the TXT versus TX was $699,976.43 in the U.S. and $90,585.57 in China, both of which are higher than their respective threshold of willingness to play. Deterministic sensitivity analysis shows that the price of tucatinib is the parameter that has the most significant impact on ICERs, but it does not change the results of the model. Probability sensitivity analysis shows that the probability of cost-effective for TXT is 0 in the base case. Conclusion: In the United States and China, tucatinib combined with trastuzumab and capecitabine is not cost-effective for patients with HER-2 positive metastatic breast cancer.
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Affiliation(s)
- Qiuji Wu
- Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.,West China Biomedical Big Data Center, Sichuan University, Chengdu, China
| | - Weiting Liao
- Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.,West China Biomedical Big Data Center, Sichuan University, Chengdu, China
| | - Mengxi Zhang
- Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.,West China Biomedical Big Data Center, Sichuan University, Chengdu, China
| | - Jiaxing Huang
- Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.,West China Biomedical Big Data Center, Sichuan University, Chengdu, China
| | - Pengfei Zhang
- Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.,West China Biomedical Big Data Center, Sichuan University, Chengdu, China
| | - Qiu Li
- Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.,West China Biomedical Big Data Center, Sichuan University, Chengdu, China
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Li J, Zhang T, Lu P, Zhao J, Chen L, Jiang J. Cost-effectiveness analysis of atezolizumab plus nab-paclitaxel for untreated metastatic triple-negative breast cancer. Immunotherapy 2020; 12:705-713. [PMID: 32522057 DOI: 10.2217/imt-2020-0036] [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: 12/17/2022] Open
Abstract
Aim: To evaluate the cost-effectiveness of atezolizumab plus nab-paclitaxel (ANP) in the first-line treatment of metastatic triple-negative breast cancer (TNBC). Materials & methods: We developed a Markov model to evaluate the cost and effectiveness of ANP versus nab-paclitaxel in the first-line treatment of metastatic TNBC. Lifetime costs, life-years (LYs) and quality-adjusted LYs (QALYs) were estimated. Results: ANP provided an additional 0.16 QALYs (0.24 LYs) compared with nab-paclitaxel in intention-to-treat population. The corresponding incremental cost-effectiveness ratio was $786,131 per QALY gained. However, the incremental cost-effectiveness ratio decreased to $361,218 per QALY gained in the PD-L1 positive subgroup analysis. Conclusion: From the perspective of a US-payer, ANP is estimated not to be cost-effective in the first-line treatment of metastatic TNBC.
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Affiliation(s)
- Jiahao Li
- College of Pharmacy, Jinan University, Guangzhou 510632, China
| | - Tiantian Zhang
- College of Pharmacy, Jinan University, Guangzhou 510632, China.,International Cooperative Laboratory of Traditional Chinese Medicine Modernization & Innovative Drug Development of Chinese Ministry of Education (MOE), Jinan University, Guangzhou 510632, China.,Guangzhou Huabo Biopharmaceutical Research Institute, 510010, China
| | - Peiyao Lu
- College of Pharmacy, Jinan University, Guangzhou 510632, China
| | - Jianfu Zhao
- Department of Oncology, The First Affiliated Hospital, Jinan University, Guangzhou 510632, China
| | - Lin Chen
- Drug Clinical Trial Institution, The First Affiliated Hospital, Jinan University, Guangzhou 510632, China
| | - Jie Jiang
- College of Pharmacy, Jinan University, Guangzhou 510632, China.,International Cooperative Laboratory of Traditional Chinese Medicine Modernization & Innovative Drug Development of Chinese Ministry of Education (MOE), Jinan University, Guangzhou 510632, China.,Dongguan Institute of Jinan University, Dongguan 523808, China
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29
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Li S, Peng L, Tan C, Zeng X, Wan X, Luo X, Yi L, Li J. Cost-Effectiveness of ramucirumab plus paclitaxel as a second-line therapy for advanced gastric or gastro-oesophageal cancer in China. PLoS One 2020; 15:e0232240. [PMID: 32379763 PMCID: PMC7205241 DOI: 10.1371/journal.pone.0232240] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2019] [Accepted: 04/11/2020] [Indexed: 12/24/2022] Open
Abstract
AIM That clinical trial (RAINBOW) showed that a 7.4 months overall survival benefit with the combination therapy with ramucirumab (RAM) and paclitaxel (PAC) as second-line therapy for patients with recurrent or metastatic gastric or gastro-oesophageal junction adenocarcinoma, compared with placebo (PLA) plus paclitaxel. We performed an analysis to assess the cost-effectiveness of RAM from a Chinese perspective and recognized the range of drug costs. METHODS By building a Markov model to estimate quality-adjusted life-years (QALYs), life-years (LYs) and lifetime costs. Transition probabilities, costs and utilities were estimated for the published literature, Chinese health care system and local price setting. We performed threshold analyses and probabilistic sensitivity analyses to evaluate the uncertainty of the model. RESULTS Compared with PLA strategy, RAM strategy provided an incremental survival benefit of 1.22 LYs and 0.64 QALYs. The probabilistic sensitivity analysis showed that when RAM costs less than $151 or $753 per 4 weeks, the incremental cost-effectiveness ratio (ICER) approximated the willingness-to-pay threshold (WTP), suggesting that there was 50% likelihood that the ICER for RAM + PAC would be less than $44528.4 per QALY or $48121 per QALY, respectively. CONCLUSIONS For patients with advanced gastric or gastro-oesophageal junction adenocarcinoma who fail first-line chemotherapy, our results are conducive to the multilateral drug price guidance negotiations of RAM in China.
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Affiliation(s)
- Sini Li
- The Xiangya Nursing School, Central South University, Changsha, Hunan, China
| | - Liubao Peng
- Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Chongqing Tan
- Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Xiaohui Zeng
- The Second Xiangya Hospital, PET-CT Center, Central South University, Changsha, Hunan, China
| | - Xiaomin Wan
- The Xiangya Nursing School, Central South University, Changsha, Hunan, China
| | - Xia Luo
- Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Lidan Yi
- Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Jianhe Li
- Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
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30
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Wu B, Ma F. Cost-effectiveness of adding atezolizumab to first-line chemotherapy in patients with advanced triple-negative breast cancer. Ther Adv Med Oncol 2020; 12:1758835920916000. [PMID: 32426048 PMCID: PMC7222249 DOI: 10.1177/1758835920916000] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2019] [Accepted: 02/26/2020] [Indexed: 12/20/2022] Open
Abstract
Background: The effectiveness of atezolizumab plus nab-paclitaxel for advanced triple-negative breast cancer (TNBC) has been demonstrated. We aimed to evaluate its cost-effectiveness on advanced TNBC from the US payer perspective. Methods: A Markov model was adopted to project the disease course of newly diagnosed advanced TNBC. The clinical data were gathered from the IMpassion130 trial. Cost and health preference data were derived from the literature. The incremental cost-effectiveness ratio (ICER) was measured, and one-way sensitivity analysis and probabilistic sensitivity analysis were performed for exploring the model uncertainties. Results: Our results demonstrated that atezolizumab plus nab-paclitaxel augmented versus nab-paclitaxel therapy cost $104,278 and $149,465 and yielded an additional 0.371 and 0.762 of quality-adjusted life year (QALY) in in all patients with unknown PD-L1 status and subpopulation with PD-L1-positive, respectively, which led to an ICER of $281,448 and $196,073 per QALY gained. In all patients with unknown PD-L1 status, atezolizumab plus nab-paclitaxel treatment guiding by PD-L1 expression testing resulted in an ICER of $183,508 per QALY gained. Atezolizumab plus nab-paclitaxel could maintain a trend of positive incremental net health benefits and >50% probabilities of cost-effectiveness at the threshold of $200,000/QALY in more than half of subgroups with PD-L1-positive. One-way and probabilistic sensitivity analyses revealed the results were most sensitive to the hazard ratios (HRs) of overall survival (OS) of atezolizumab plus nab-paclitaxel versus nab-paclitaxel treatment. Conclusion: The atezolizumab plus nab-paclitaxel treatment is likely to be a cost-effective option compared with chemotherapy based on nab-paclitaxel for the patients with PD-L1-positive advanced TNBC.
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Affiliation(s)
- Bin Wu
- Department of Pharmacy, Ren Ji Hospital, South Campus, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | - Fei Ma
- Department of Medical Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17 Panjiayuan Road, Chaoyang District, Beijing 100021, China
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Rahardja S, Tan RYC, Sultana R, Leong FL, Lim EH. Efficacy, patterns of use and cost of Pertuzumab in the treatment of HER2+ metastatic breast cancer in Singapore: The National Cancer Centre Singapore experience. World J Clin Oncol 2020; 11:143-151. [PMID: 32257845 PMCID: PMC7103528 DOI: 10.5306/wjco.v11.i3.143] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2019] [Revised: 12/06/2019] [Accepted: 02/23/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Pertuzumab is a humanized anti-human epidermal growth factor receptor 2 (HER2) monoclonal antibody found in a Phase III clinical trial to significantly improve median survival in HER2 positive metastatic breast cancer (MBC) when used in combination with a taxane and Trastuzumab, and its clinical efficacy has transformed the therapeutic landscape of HER2-positive breast cancer. There are currently few reports on the pattern of use and value of Pertuzumab in real world settings. Our study describes the clinical efficacy and treatment costs of Pertuzumab in HER2-positive MBC treated in a tertiary cancer centre in Singapore in a predominantly Asian population.
AIM To investigate the clinical efficacy and treatment costs of Pertuzumab in HER2-positive MBC in an Asian population in Singapore.
METHODS A retrospective study of 304 HER2-positive MBC patients seen at National Cancer Centre Singapore between 2011-2017 was conducted. Demographic and clinical data were extracted from electronic medical records. Clinical characteristics and billing data of patients who received Pertuzumab were compared with those who did not.
RESULTS Thirty-one (62.0%) of the fifty (16.4%) patients who received Pertuzumab as first-line therapy. With a median follow-up of 21.5 mo, there was a statistically significant difference in the median overall survival between Pertuzumab and non-Pertuzumab groups [51.5 (95%CI: 35.8–60.0) vs 32.9 (95%CI: 28.1–37.5) mo; P = 0.0128]. Two (4.88%) patients in the Pertuzumab group experienced grade 3 (G3) cardiotoxicity. The median treatment cost incurred for total chemotherapy for the Pertuzumab group was 130456 Singapore Dollars compared to 34523 Singapore Dollars for the non-Pertuzumab group. The median percentage of total chemotherapy costs per patient in the Pertuzumab group spent on Pertuzumab was 50.3%.
CONCLUSION This study shows that Pertuzumab use in the treatment of metastatic breast cancer is associated with a significantly better survival and a low incidence of serious cardiotoxicity. However, the proportionate cost of Pertuzumab therapy remains high and further cost-effectiveness studies should be conducted.
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Affiliation(s)
- Sylwan Rahardja
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore
| | | | | | - Fun Loon Leong
- National Cancer Centre Singapore, Singapore 169610, Singapore
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Gad M, Salem A, Oortwijn W, Hill R, Godman B. Mapping of Current Obstacles for Rationalizing Use of Medicines (CORUM) in Europe: Current Situation and Potential Solutions. Front Pharmacol 2020; 11:144. [PMID: 32194401 PMCID: PMC7063972 DOI: 10.3389/fphar.2020.00144] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2019] [Accepted: 02/04/2020] [Indexed: 01/01/2023] Open
Abstract
Introduction There are increasing concerns regarding the inappropriate use of medicines with expenditure continuing to grow driven by increasing sales in oncology and orphan diseases, enhanced by their emotive nature. As a result, even high income countries are struggling to fund new premium priced medicines. These concerns have resulted in initiatives to better manage the entry of new medicines and enhance the rational use of medicines (RUM). However, there is a need to ascertain the current situation. We sought to address this by developing the Current Obstacles for Rationalizing Use of Medicines in Europe (CORUM) mapping tool to qualitatively investigate the current situation and provide analysis of current views on RUM and interventions among key European payers and their advisers. The findings will be used to provide future guidance. Methodology Descriptive study exploring and identifying perceived gaps to achieving optimal RUM. The CORUM tool was based on the WHO 12 key interventions to promote RUM. Results 62 participants took part with most respondents believing their country could improve RUM capacity. This included educational initiatives on the use of clinical guidelines (90%) and the inclusion of problem-based pharmacotherapy in undergraduate curricula and for Continued Professional Development. Key challenges included a lack of regular updates of guidelines, exacerbated by limited funding and a lack of follow-up to monitor adherence to agreed guidelines. RUM could also be enhanced by the development of regional formularies as well as implementing Drug and Therapeutic Committees where these are currently limited. There also needs to be greater co-ordination between RUM and Health Technology Assessment activities, with countries learning from each other. Conclusion There is an urgent need to improve RUM through improved educational and other activities among European countries, with countries learning from each other. This will involve addressing current challenges and we will be following this up.
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Affiliation(s)
- Mohamed Gad
- Global Health and Development Group, Imperial College London, London, United Kingdom
| | - Ahmed Salem
- Real World Evidence Solutions, IQVIA, Zaventem, Belgium
| | - Wija Oortwijn
- Department for Health Evidence, Radboud University Medical Center, Nijmegen, Netherlands
| | - Ruaraidh Hill
- Liverpool Reviews and Implementation Group, University of Liverpool, Liverpool, United Kingdom
| | - Brian Godman
- Department of Laboratory Medicine, Division of Clinical Pharmacology, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.,Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom.,Health Economics Centre, University of Liverpool Management School, Liverpool, United Kingdom.,Department of Public Health Pharmacy and Management, School of Pharmacy, Sefako Makgatho Health Sciences University, Garankuwa, South Africa
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Cortes J, Perez-García JM, Llombart-Cussac A, Curigliano G, El Saghir NS, Cardoso F, Barrios CH, Wagle S, Roman J, Harbeck N, Eniu A, Kaufman PA, Tabernero J, García-Estévez L, Schmid P, Arribas J. Enhancing global access to cancer medicines. CA Cancer J Clin 2020; 70:105-124. [PMID: 32068901 DOI: 10.3322/caac.21597] [Citation(s) in RCA: 124] [Impact Index Per Article: 24.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Globally, cancer is the second leading cause of death, with numbers greatly exceeding those for human immunodeficiency virus/acquired immunodeficiency syndrome, tuberculosis, and malaria combined. Limited access to timely diagnosis, to affordable, effective treatment, and to high-quality care are just some of the factors that lead to disparities in cancer survival between countries and within countries. In this article, the authors consider various factors that prevent access to cancer medicines (particularly access to essential cancer medicines). Even if an essential cancer medicine is included on a national medicines list, cost might preclude its use, it might be prescribed or used inappropriately, weak infrastructure might prevent it being accessed by those who could benefit, or quality might not be guaranteed. Potential strategies to address the access problems are discussed, including universal health coverage for essential cancer medicines, fairer methods for pricing cancer medicines, reducing development costs, optimizing regulation, and improving reliability in the global supply chain. Optimizing schedules for cancer therapy could reduce not only costs, but also adverse events, and improve access. More and better biomarkers are required to target patients who are most likely to benefit from cancer medicines. The optimum use of cancer medicines depends on the effective delivery of several services allied to oncology (including laboratory, imaging, surgery, and radiotherapy). Investment is necessary in all aspects of cancer care, from these supportive services to technologies, and the training of health care workers and other staff.
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Affiliation(s)
- Javier Cortes
- IOB Institute of Oncology, Quironsalud Group, Madrid, Spain
- IOB Institute of Oncology, Quironsalud Group, Hospital Quiron, Barcelona, Spain
- Medica Scientia Innovation Research, Barcelona, Spain
- Vall d'Hebron Institute of Oncology, Barcelona, Spain
| | - Jose Manuel Perez-García
- IOB Institute of Oncology, Quironsalud Group, Hospital Quiron, Barcelona, Spain
- Medica Scientia Innovation Research, Barcelona, Spain
| | | | | | - Nagi S El Saghir
- Division of Hematology Oncology, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon
| | - Fatima Cardoso
- Breast Unit, Champalimaud Clinical Center/Champalimaud Foundation, Lisbon, Portugal
| | - Carlos H Barrios
- Oncology Research Center, Hospital Sao Lucas, Porto Alegre, Brazil
| | | | - Javier Roman
- Breast Unit, Gastrointestinal Tumor Unit and Lung Tumor Unit, IOB Institute of Oncology, Quironsalud Group, Madrid, Spain
| | - Nadia Harbeck
- Breast Center, Department of Obstetrics and Gynecology, University of Munich (LMU), Munich, Germany
| | | | | | - Josep Tabernero
- IOB Institute of Oncology, Quironsalud Group, Hospital Quiron, Barcelona, Spain
- Medical Oncology Department, Vall d'Hebron Institute of Oncology, CIBERONC, Barcelona, Spain
| | | | - Peter Schmid
- Center of Experimental Cancer Medicine, Barts Cancer Institute, St. Bartholomew Breast Cancer Center, St. Bartholomew's Hospital, London, United Kingdom
| | - Joaquín Arribas
- Preclinical Research Program, Vall d'Hebron Institute of Oncology, Barcelona, Spain
- Biomedical Research Oncology Network (CIBERONC), Barcelona, Spain
- Department of Biochemistry and Molecular Biology, Autonomous University of Barcelona, Bellaterra, Spain
- Catalan Institution for Research and Advanced Studies, (ICREA), Barcelona, Spain
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Pontes C, Zara C, Torrent-Farnell J, Obach M, Nadal C, Vella-Bonanno P, Ermisch M, Simoens S, Hauegen RC, Gulbinovic J, Timoney A, Martin AP, Mueller T, Nachtnebel A, Campbell S, Selke G, Bochenek T, Rothe CC, Mardare I, Bennie M, Fürst J, Malmstrom RE, Godman B. Time to Review Authorisation and Funding for New Cancer Medicines in Europe? Inferences from the Case of Olaratumab. APPLIED HEALTH ECONOMICS AND HEALTH POLICY 2020; 18:5-16. [PMID: 31696433 DOI: 10.1007/s40258-019-00527-x] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/10/2023]
Abstract
The potential benefits of early patient access to new medicines in areas of high unmet medical need are recognised, but uncertainties concerning effectiveness, safety and added value when new medicines are authorised, and subsequently funded based on initial preliminary data only, have important implications. In 2016 olaratumab received accelerated conditional approval from both the European Medicines Agency and the US Food and Drug Administration for the treatment of soft-tissue sarcoma, based on the claims of a substantial reduction in the risk of death with an 11.8-month improvement in median overall survival in a phase II trial in combination with doxorubicin vs. doxorubicin alone. The failure to confirm these benefits in the post-authorisation pivotal trial has highlighted key concerns regarding early access and conditional approvals for new medicines. Concerns include potentially considerable clinical and economic costs, so that patients may have received suboptimal treatment and any money spent has foregone the opportunity to improve access to effective treatments. As a result, it seems reasonable to reconsider current marketing authorisation models and approaches. Potential pathways forward include closer collaboration between regulators, pharmaceutical companies and payers to enhance the generation of rapid and comparative confirmatory trials in a safe and fair manner, with minimal patient exposure as required to achieve robust evidence. Additionally, it may be time to review early access systems, and to explore new avenues regarding who should pay or part pay for new treatments whilst information is being collected as part of any obligations for conditional marketing authorisation. Greater co-operation between countries regarding the collection of data in routine clinical care, and further research on post-marketing data analysis and interpretation, may also contribute to improved appraisal and continued access to new innovative cancer treatments.
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Affiliation(s)
- Caridad Pontes
- Drug Area, Catalan Health Service, Travessera de les Corts 131, Edifici Olimpia, 08028, Barcelona, Spain.
- Department of Pharmacology, Therapeutics and Toxicology, Universitat Autònoma de Barcelona, Barcelona, Spain.
| | - Corinne Zara
- Drug Area, Catalan Health Service, Travessera de les Corts 131, Edifici Olimpia, 08028, Barcelona, Spain
| | - Josep Torrent-Farnell
- Drug Area, Catalan Health Service, Travessera de les Corts 131, Edifici Olimpia, 08028, Barcelona, Spain
- Department of Pharmacology, Therapeutics and Toxicology, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Merce Obach
- Drug Area, Catalan Health Service, Travessera de les Corts 131, Edifici Olimpia, 08028, Barcelona, Spain
| | | | - Patricia Vella-Bonanno
- Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK
| | - Michael Ermisch
- Pharmaceutical Department, National Association of Statutory Health Insurance Funds, Berlin, Germany
| | - Steven Simoens
- Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium
| | - Renata Curi Hauegen
- National Institute of Science and Technology for Innovation on Diseases of Neglected Populations (INCT-IDPN), Center for Technological Development in Health (CDTS), Osvaldo Cruz Foundation (Fiocruz), Rio de Janeiro, Brazil
| | - Jolanta Gulbinovic
- Department of Pathology, Forensic Medicine and Pharmacology, Institute of Biomedical Sciences, Faculty of Medicine, Vilnius University, Vilnius, Lithuania
| | - Angela Timoney
- Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK
- NHS Lothian, Edinburgh, UK
| | - Antony P Martin
- Health Economics Centre, University of Liverpool Management School, Liverpool, UK
| | - Tanja Mueller
- Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK
| | - Anna Nachtnebel
- Hauptverband der Österreichischen Sozialversicherungsträger, Vienna, Austria
| | - Stephen Campbell
- Centre for Primary Care, Division of Population Health, Health Services Research and Primary Care, University of Manchester, Manchester, UK
- NIHR Greater Manchester Patient Safety Translational Research Centre, School of Health Sciences, University of Manchester, Manchester, UK
| | - Gisbert Selke
- Wissenschaftliches Institut der AOK (WidO), Berlin, Germany
| | - Tomasz Bochenek
- Department of Drug Management, Faculty of Health Sciences, Jagiellonian University Medical College, Kraków, Poland
| | - Celia C Rothe
- Department of Drug Management, Faculty of Health Sciences, Jagiellonian University Medical College, Kraków, Poland
| | - Ileana Mardare
- Department of Public Health and Management, Faculty of Medicine, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania
| | - Marion Bennie
- Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK
| | - Jurij Fürst
- Health Insurance Institute, Ljubljana, Slovenia
| | - Rickard E Malmstrom
- Department of Medicine Solna, Karolinska Institute, Karolinska University Hospital Solna, Stockholm, Sweden
| | - Brian Godman
- Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK
- Health Economics Centre, University of Liverpool Management School, Liverpool, UK
- Division of Clinical Pharmacology, Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden
- School of Pharmacy, Sefako Makgatho Health Sciences University, Ga-Rankuwa, South Africa
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Jayasekera J, Mandelblatt JS. Systematic Review of the Cost Effectiveness of Breast Cancer Prevention, Screening, and Treatment Interventions. J Clin Oncol 2020; 38:332-350. [PMID: 31804858 PMCID: PMC6994253 DOI: 10.1200/jco.19.01525] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/10/2019] [Indexed: 12/12/2022] Open
Affiliation(s)
- Jinani Jayasekera
- Georgetown-Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC
| | - Jeanne S. Mandelblatt
- Georgetown-Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC
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First-line fulvestrant plus anastrozole for hormone-receptor-positive metastatic breast cancer in postmenopausal women: a cost-effectiveness analysis. Breast Cancer 2019; 27:399-404. [PMID: 31853795 DOI: 10.1007/s12282-019-01034-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2019] [Accepted: 12/04/2019] [Indexed: 02/05/2023]
Abstract
PURPOSE In a recent randomized, open-label trial (S0226), the addition of fulvestrant to anastrozole therapy decreased the risk of progression and death in patients with hormone-receptor-positive metastatic breast cancer. However, the cost-effectiveness of incorporating fulvestrant into the first-line setting is unknown. METHODS We developed a Markov model to assess the costs and clinical outcomes of fulvestrant plus anastrozole compared with anastrozole as a first-line therapy in a cohort of patients with advanced hormone-receptor-positive breast cancer. The transition probabilities were estimated from the fitted survival curves in the S0226 trial. Health care costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated for fulvestrant plus anastrozole compared with anastrozole from US payer's perspective. RESULTS Fulvestrant plus anastrozole led to an improvement of 0.11 QALYs compared with treatment with anastrozole alone. However, incorporating fulvestrant into the first-line therapy produced significantly higher health care costs ($72,496 vs. $38,959 for all eligible patients, and $73,728 vs. $37,239 for patients with no previous hormonal adjuvant therapy), resulting in ICERs of $300,564 and $194,450/QALY, respectively. Two-way sensitivity analysis showed that when the cost of fulvestrant decreased to $1.5/mg for all eligible patients or $3.5/mg for patients with no previous hormonal adjuvant therapy, at the perfect health in progression-free status, the ICER became $141,320 and $145,543 per QALY. CONCLUSION Substituting fulvestrant as a first-line therapy for hormone-receptor-positive metastatic breast cancer is not cost-effective compared with anastrozole based on the willing-to-pay threshold of $150,000 per QALY.
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37
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Jeon SH, Pohl RV. Medical innovation, education, and labor market outcomes of cancer patients. JOURNAL OF HEALTH ECONOMICS 2019; 68:102228. [PMID: 31521025 DOI: 10.1016/j.jhealeco.2019.102228] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/07/2019] [Revised: 08/19/2019] [Accepted: 08/19/2019] [Indexed: 06/10/2023]
Abstract
Innovations in cancer treatment have lowered mortality, but little is known about their economic benefits. We assess the effect of two decades of improvement in cancer treatment options on the labor market outcomes of breast and prostate cancer patients. In addition, we compare this effect across cancer patients with different levels of educational attainment. We estimate the effect of medical innovation on cancer patients' labor market outcomes employing tax return and cancer registry data from Canada and measuring medical innovation by using the number of approved drugs and a quality-adjusted patent index. We find that innovations in cancer treatment during the 1990s and 2000s reduced the negative employment effects of cancer by 63% to 70%, corresponding to a reduction in the economic costs of prostate and breast cancer diagnoses by 13,500 and 5800 dollars per year, respectively. The benefits of medical innovation are limited to cancer patients with postsecondary education.
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Affiliation(s)
- Sung-Hee Jeon
- Statistics Canada, Social Analysis and Modelling Division, R.H. Coats Building, Ottawa, ON K1A 0T6, Canada.
| | - R Vincent Pohl
- University of Georgia, Terry College of Business, Department of Economics, 620 S Lumpkin St, Athens, GA 30602, USA.
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Ishii K, Morii N, Yamashiro H. Pertuzumab in the treatment of HER2-positive breast cancer: an evidence-based review of its safety, efficacy, and place in therapy. CORE EVIDENCE 2019; 14:51-70. [PMID: 31802990 PMCID: PMC6827570 DOI: 10.2147/ce.s217848] [Citation(s) in RCA: 51] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/31/2019] [Accepted: 08/01/2019] [Indexed: 12/23/2022]
Abstract
Human epidermal growth factor receptor 2 (HER2)-positive breast cancer is a distinct subset of breast cancer that results from overexpression of HER2 protein. Pertuzumab-a recombinant humanized monoclonal antibody that binds to the extracellular dimerization domain II of HER2-was recently approved for adjuvant therapy and neoadjuvant therapy of HER2-positive early breast cancer. As pertuzumab and trastuzumab bind to different domains of the extracellular dimerization domain of HER2, a combination therapy of pertuzumab and trastuzumab is beneficial for the treatment of metastatic cancer, advanced local cancer, or early cancer by dual HER2 blockage. Many clinical trials have been performed using pertuzumab for breast cancer patients; these include the CLEOPATRA trial for palliative therapy, the APHINITY trial for adjuvant therapy, and the NeoSphere and the TRYPHAENA trials for neoadjuvant therapy. These trials revealed pertuzumab to be a safe and effective drug regardless of the patient age and hormone receptor status. Notably, pertuzumab use was associated with severe cardiac toxicity in some cases; however, the risk of pertuzumab-induced cardiac dysfunction was low. The most common adverse effect associated with pertuzumab-use was diarrhea, but most cases were not severe. Several different chemotherapeutic agents have been investigated to determine optimal chemotherapeutic combinations for dual HER2 blockage. Some exploratory analyses indicate that pertuzumab treatment offered little benefit to patients with node-negative and small primary tumors; pertuzumab treatment was also found not be cost-effective. Further research will reveal the appropriate usage of pertuzumab for treating a subset of eligible patients.
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Affiliation(s)
- Kei Ishii
- Department of Breast Surgery, Tenri Hospital, Tenri, Japan
| | - Nao Morii
- Department of Breast Surgery, Tenri Hospital, Tenri, Japan
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Schwartz NR, Flanagan MR, Babigumira JB, Steuten LM, Roth JA. Cost-Effectiveness Analysis of Adjuvant Neratinib Following Trastuzumab in Early-Stage HER2-Positive Breast Cancer. J Manag Care Spec Pharm 2019; 25:1133-1139. [PMID: 31556818 PMCID: PMC10398073 DOI: 10.18553/jmcp.2019.25.10.1133] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
BACKGROUND Disease-free survival (DFS) in early-stage human epidermal growth factor receptor 2 (HER2)-positive breast cancer is significantly greater with the addition of neratinib after adjuvant trastuzumab versus no additional therapy. However, it remains uncertain whether these survival gains represent good value for the money, given the substantial cost of neratinib. OBJECTIVE To evaluate clinical and economic implications of adding neratinib after adjuvant trastuzumab based on results from the phase III ExteNET trial. METHODS A 3-state Markov model was developed to estimate the cost-effectiveness of neratinib for women with early-stage (I-III) HER2-positive breast cancer. Five-year recurrence rates were derived from the ExteNET trial. Mortality and recurrence rates after 5 years were derived from the HERceptin Adjuvant (HERA) trial. Outcomes included life-years, quality-adjusted life-years (QALYs), and direct medical expenditures. The analysis was performed from a payer perspective over a lifetime horizon. One-way sensitivity and probabilistic analyses were conducted to evaluate uncertainty. RESULTS Total cost of neratinib following adjuvant trastuzumab was $317,619 versus $152,812 for adjuvant trastuzumab alone. A gain of 0.4 QALYs (15.7 vs. 15.3) and 0.1 years of projected life expectancy (18.3 vs. 18.2) favored neratinib after trastuzumab versus trastuzumab alone. The neratinib cost per QALY gained was $416,106. At standard willingness-to-pay thresholds of $50,000, $100,000, and $200,000 per QALY gained, neratinib has a probability of 2.8%, 16.7%, and 33.9% of cost-effectiveness, respectively. The cost per QALY gained in a scenario analysis only including patients with hormone-receptor positive disease was $275,311. CONCLUSIONS Based on 5-year data from ExteNET, neratinib following adjuvant trastuzumab is not projected to be cost-effective, even among those patients shown to derive the greatest clinical benefit. Future analyses should reassess the cost-effectiveness associated with neratinib treatment as trial data mature. DISCLOSURES No outside funding supported this study. Roth reports consulting fees from Genentech. Steuten reports grants from AstraZeneca, EMD Serono, and Genomic Health, along with personal fees from Agendia, unrelated to this study. The other authors have no conflicts of interest in connection with this study.
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Affiliation(s)
- Naomi R.M. Schwartz
- The Comparative Health Outcomes, Policy, and Economics (CHOICE) Institute, University of Washington, Seattle
| | - Meghan R. Flanagan
- Department of Surgery, University of Washington School of Medicine, and Fred Hutchinson Cancer Research Center, Seattle, Washington
| | | | - Lotte M. Steuten
- Office of Health Economics, London, United Kingdom, and Fred Hutchinson Cancer Research Center, Seattle, Washington
| | - Joshua A. Roth
- Fred Hutchinson Cancer Research Center, Seattle, Washington
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40
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Viale G, Morganti S, Ferraro E, Zagami P, Marra A, Curigliano G. What therapies are on the horizon for HER2 positive breast cancer? Expert Rev Anticancer Ther 2019; 19:811-822. [PMID: 31448640 DOI: 10.1080/14737140.2019.1660164] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Introduction: Despite dramatic improvements in survival achieved with currently available anti-HER2 agents, HER2-positive metastatic breast cancer remains an almost invariably deadly disease, with primary or acquired resistance to HER2-directed agents developing during treatment. Many efforts are focused on identifying new agents that may more effectively inhibit HER2 signaling and on possible combination strategies. Areas covered: This review summarizes the landscape of drugs under development for HER2-positive metastatic breast cancer, as antibody-drug conjugates, monoclonal anti-HER2 antibodies, bispecific antibodies, or novel tyrosine kinase inhibitors. Moreover, available data for possible combination of anti-HER2 drugs and different agents, as immunotherapy, PI3K/mTOR inhibitors, CDK4/6 inhibitors currently under evaluation are reviewed. These strategies may overcome mechanisms of resistance and further improve patient outcomes. Expert opinion: Identification of valuable predictive biomarkers is needed to better inform choice of treatment sequence for the individual patient and limit the financial toxicity of these agents.
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Affiliation(s)
- Giulia Viale
- Division of Early Drug Development for Innovative Therapy, IEO, European Institute of Oncology IRCCS , Milan , Italy.,Department of Oncology and Haematology, University of Milan , Milan , Italy
| | - Stefania Morganti
- Division of Early Drug Development for Innovative Therapy, IEO, European Institute of Oncology IRCCS , Milan , Italy.,Department of Oncology and Haematology, University of Milan , Milan , Italy
| | - Emanuela Ferraro
- Division of Early Drug Development for Innovative Therapy, IEO, European Institute of Oncology IRCCS , Milan , Italy.,Department of Oncology and Haematology, University of Milan , Milan , Italy
| | - Paola Zagami
- Division of Early Drug Development for Innovative Therapy, IEO, European Institute of Oncology IRCCS , Milan , Italy.,Department of Oncology and Haematology, University of Milan , Milan , Italy
| | - Antonio Marra
- Division of Early Drug Development for Innovative Therapy, IEO, European Institute of Oncology IRCCS , Milan , Italy.,Department of Oncology and Haematology, University of Milan , Milan , Italy
| | - Giuseppe Curigliano
- Division of Early Drug Development for Innovative Therapy, IEO, European Institute of Oncology IRCCS , Milan , Italy.,Department of Oncology and Haematology, University of Milan , Milan , Italy
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Battisti NML, Tong D, Ring A, Smith I. Long-term outcome with targeted therapy in advanced/metastatic HER2-positive breast cancer: The Royal Marsden experience. Breast Cancer Res Treat 2019; 178:401-408. [DOI: 10.1007/s10549-019-05406-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2019] [Accepted: 08/09/2019] [Indexed: 10/26/2022]
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Eiger D, Pondé NF, de Azambuja E. Pertuzumab in HER2-positive early breast cancer: current use and perspectives. Future Oncol 2019; 15:1823-1843. [PMID: 30938542 DOI: 10.2217/fon-2018-0896] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Although the prognosis of HER2-positive breast cancer patients has dramatically improved with modern chemotherapy and the monoclonal antibody trastuzumab, up to 31% of them will experience a recurrence in the long term. After the unprecedented benefit in overall survival with the addition of the second monoclonal antibody pertuzumab for patients with metastatic disease, the drug was tested with various degrees of success in the preoperative and postoperative settings. In this review, we will focus on the pharmacologic aspects of the drug, including mechanism of action and toxicities, and discuss clinical data regarding its use in advanced and early stage HER2-positive breast cancer, placing in perspective the pros and cons regarding other available drugs and biomarkers.
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Affiliation(s)
- Daniel Eiger
- Institut Jules Bordet - Université Libre de Bruxelles (ULB); Medical Oncology Department, Academic Promoting Team at Boulevard de Waterloo, 121, 1000, Brussels, Belgium
| | - Noam Falbel Pondé
- Institut Jules Bordet - Université Libre de Bruxelles (ULB); Medical Oncology Department, Academic Promoting Team at Boulevard de Waterloo, 121, 1000, Brussels, Belgium
| | - Evandro de Azambuja
- Institut Jules Bordet - Université Libre de Bruxelles (ULB); Medical Oncology Department, Academic Promoting Team at Boulevard de Waterloo, 121, 1000, Brussels, Belgium
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Garrison LP, Babigumira J, Tournier C, Goertz HP, Lubinga SJ, Perez EA. Cost-Effectiveness Analysis of Pertuzumab With Trastuzumab and Chemotherapy Compared to Trastuzumab and Chemotherapy in the Adjuvant Treatment of HER2-Positive Breast Cancer in the United States. VALUE IN HEALTH : THE JOURNAL OF THE INTERNATIONAL SOCIETY FOR PHARMACOECONOMICS AND OUTCOMES RESEARCH 2019; 22:408-415. [PMID: 30975391 DOI: 10.1016/j.jval.2018.11.014] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/12/2018] [Revised: 09/17/2018] [Accepted: 11/17/2018] [Indexed: 06/09/2023]
Abstract
OBJECTIVE The APHINITY trial assessed the effectiveness and the safety of adding pertuzumab to trastuzumab and chemotherapy (THP) compared to trastuzumab and chemotherapy (TH) in the adjuvant management of human epidermal growth factor 2-positive (HER2+) breast cancer. We performed a study to project the potential cost-effectiveness of THP vs. TH. STUDY DESIGN Trial-based cost-utility modeling analysis. METHODS We performed an economic evaluation from a payer perspective using a Markov model with six health states: invasive disease-free survival, non-metastatic recurrence, remission, first-line metastatic, subsequent line metastatic, and death. We parameterized the model using data from both arms in APHINITY extrapolated to a patient's lifetime horizon. Estimates of health state utilities were based on EQ-5D trial data and the literature, and costs were estimated from government sources and the published literature. The primary outcomes of the model were life-years (LYs), quality-adjusted LYs (QALYs), costs, and incremental cost-effectiveness ratios (ICERs). Uncertainty was addressed via univariate and probabilistic sensitivity analyses. RESULTS For the intention-to-treat population, the model projected improved outcomes (by 0.50 LYs and 0.45 QALYs) and increased costs (by $74 420) for ICERs of $147 774/LY gained and $167 185/QALY gained for PHT vs. HT patients. In the node-positive patient population, the model projected improved outcomes (by 0.86 LYs and 0.76 QALYs) and increased costs (by $66 647) for ICERs of $77 684/LY gained and $87 929/QALY gained. For the hormone-receptor-negative patient population, the model projected health gains, increased costs, and ICERs of $147 022/LY gained and $166 518/QALY gained. The results were sensitive to changes in the model time horizon. CONCLUSION The addition of pertuzumab to the available regimens for HER2+ early breast cancer is likely to be cost-effective for patients in the U.S. at high risk of recurrence.
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MESH Headings
- Aged
- Aged, 80 and over
- Antibodies, Monoclonal, Humanized/administration & dosage
- Antibodies, Monoclonal, Humanized/adverse effects
- Antibodies, Monoclonal, Humanized/economics
- Antineoplastic Agents, Immunological/administration & dosage
- Antineoplastic Agents, Immunological/adverse effects
- Antineoplastic Agents, Immunological/economics
- Antineoplastic Combined Chemotherapy Protocols/adverse effects
- Antineoplastic Combined Chemotherapy Protocols/economics
- Antineoplastic Combined Chemotherapy Protocols/therapeutic use
- Breast Neoplasms/drug therapy
- Breast Neoplasms/economics
- Breast Neoplasms/enzymology
- Breast Neoplasms/mortality
- Chemotherapy, Adjuvant/economics
- Cost Savings
- Cost-Benefit Analysis
- Disease Progression
- Disease-Free Survival
- Drug Costs
- Female
- Humans
- Markov Chains
- Middle Aged
- Models, Economic
- Neoplasm Metastasis
- Neoplasm Recurrence, Local
- Quality of Life
- Quality-Adjusted Life Years
- Randomized Controlled Trials as Topic
- Receptor, ErbB-2/antagonists & inhibitors
- Receptor, ErbB-2/metabolism
- Time Factors
- Trastuzumab/administration & dosage
- Trastuzumab/adverse effects
- Trastuzumab/economics
- Treatment Outcome
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Affiliation(s)
- Louis P Garrison
- The Comparative Health Outcomes, Policy & Economics (CHOICE) Institute, Department of Pharmacy, University of Washington, Seattle, WA, USA; VeriTech Corporation, Mercer Island, WA, USA.
| | - Joseph Babigumira
- The Comparative Health Outcomes, Policy & Economics (CHOICE) Institute, Department of Pharmacy, University of Washington, Seattle, WA, USA
| | | | | | - Solomon J Lubinga
- The Comparative Health Outcomes, Policy & Economics (CHOICE) Institute, Department of Pharmacy, University of Washington, Seattle, WA, USA
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Gogate A, Rotter JS, Trogdon JG, Meng K, Baggett CD, Reeder-Hayes KE, Wheeler SB. An updated systematic review of the cost-effectiveness of therapies for metastatic breast cancer. Breast Cancer Res Treat 2019; 174:343-355. [PMID: 30603995 PMCID: PMC6705146 DOI: 10.1007/s10549-018-05099-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2018] [Accepted: 12/12/2018] [Indexed: 12/15/2022]
Abstract
PURPOSE The goal of this systematic review is to provide an update to the review by Pouwels et al. by conducting a systematic review and an assessment of the reporting quality of the economic analyses conducted since 2014. METHODS This systematic review identified published articles focused on metastatic breast cancer treatment using the Medline/PubMed and Scopus databases and the following search criteria: (((cost effectiveness[MeSH Terms]) OR (cost effectiveness) OR (cost-effectiveness) OR (cost utility) OR (cost-utility) OR (economic evaluation)) AND (("metastatic breast cancer") OR ("advanced breast cancer"))). The reporting quality of the included articles was evaluated using the International Society of Pharmacoeconomics and Outcomes Research (ISPOR) Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. RESULTS Of the 256 identified articles, 67 of the articles were published after October 2014 when the prior systematic review stopped its assessment (Pouwels et al. in Breast Cancer Res Treat 165:485-498, 2017). From the 67 articles, we narrowed down to include 17 original health economic analyses specific to metastatic or advanced breast cancer. These articles were diverse with respect to methods employed and interventions included. CONCLUSION Although each of the articles contributed their own analytic strengths and limitations, the overall quality of the studies was moderate. The review demonstrated that the vast majority of the reported incremental cost-effectiveness ratios exceeded the typically employed willingness to pay thresholds used in each country of analysis. Only three of the reviewed articles studied chemotherapies rather than treatments targeting either HER2 or hormone receptors, demonstrating a gap in the literature.
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Affiliation(s)
- Anagha Gogate
- Department of Health Policy and Management, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, 27599, USA.
| | - Jason S Rotter
- Department of Health Policy and Management, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, 27599, USA
| | - Justin G Trogdon
- Department of Health Policy and Management, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, 27599, USA
- Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA
| | - Ke Meng
- Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA
| | - Christopher D Baggett
- Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA
- Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA
| | - Katherine E Reeder-Hayes
- Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA
- Division of Hematology/Oncology, University of North Carolina, Chapel Hill, NC, USA
| | - Stephanie B Wheeler
- Department of Health Policy and Management, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, 27599, USA
- Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA
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45
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Robert M, Frenel JS, Bourbouloux E, Berton Rigaud D, Patsouris A, Augereau P, Gourmelon C, Campone M. Pertuzumab for the treatment of breast cancer. Expert Rev Anticancer Ther 2019; 20:85-95. [PMID: 30884986 DOI: 10.1080/14737140.2019.1596805] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
Introduction: Pertuzumab, a humanized monoclonal antibody that binds the human epidermal growth factor receptor 2 (HER2), inhibits the heterodimerization of HER2 with other HER receptors. It has been approved both by the Food and Drug Administration and the European Medicine Agency in the metastatic, neoadjuvant and adjuvant setting.Areas covered: This review analyses and discusses preclinical and clinical studies of pertuzumab in breast cancer. In this article, we review the status of pertuzumab, the completed and ongoing trials, and its safety.Expert opinion: Pertuzumab is a key drug for the treatment of HER2-positive metastatic or early breast cancer. However, it is imperative to identify patients that will need dual-targeting and mechanisms of resistance. Moreover, the value of pertuzumab beyond progression needs to be evaluated.
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Affiliation(s)
- Marie Robert
- Medical Oncology, Institut de Cancérologie de l'Ouest, René Gauducheau, St Herblain, France
| | - Jean-Sébastien Frenel
- Medical Oncology, Institut de Cancérologie de l'Ouest, René Gauducheau, St Herblain, France
| | - Emmanuelle Bourbouloux
- Medical Oncology, Institut de Cancérologie de l'Ouest, René Gauducheau, St Herblain, France
| | | | - Anne Patsouris
- Medical Oncology, Institut de Cancérologie de l'Ouest, Paul Papin, Angers, France
| | - Paule Augereau
- Medical Oncology, Institut de Cancérologie de l'Ouest, Paul Papin, Angers, France
| | - Carole Gourmelon
- Medical Oncology, Institut de Cancérologie de l'Ouest, René Gauducheau, St Herblain, France
| | - Mario Campone
- Medical Oncology, Institut de Cancérologie de l'Ouest, René Gauducheau, St Herblain, France.,Medical Oncology, Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Nantes, France
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Dhanushkodi M, Iyer P, Ananthi B, Krishnamurthy A. Pathological Complete Response (PCR) with TDM1 (Trastuzumab Emtansine) in Refractory HER2-Positive Locally Advanced Breast Cancer (LABC). INDIAN JOURNAL OF GYNECOLOGIC ONCOLOGY 2019. [DOI: 10.1007/s40944-018-0250-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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Geldof T, Rawal S, Dyck WV, Huys I. Comparative and combined effectiveness of innovative therapies in cancer: a literature review. J Comp Eff Res 2019; 8:205-216. [PMID: 30616358 DOI: 10.2217/cer-2018-0131] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
To achieve therapeutic innovation in oncology, already expensive novel medicines are often concomitantly combined to potentially enhance effectiveness. While this aggravates the pricing problem, comparing effectiveness of novel yet expensive (concomitant) treatments is much needed for healthcare decision-making to deliver effective but affordable treatments. This study reviewed published clinical trials and real-world studies of targeted and immune therapies. In total, 48 studies compared and/or combined multiple novel products on breast, colorectal, lung and melanoma cancers. To a great extent, products evaluated in each study were owned by one manufacturer. However, cross-manufacturer assessments are also needed. Next to costs and intensive market competition, the absence of a regulatory framework enforcing real-world multiproduct studies prevents these from being conducted. Trusted third parties could facilitate such real-world studies, for which appropriate and efficient data access is needed.
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Affiliation(s)
- Tine Geldof
- Healthcare Management Centre, Vlerick Business School, Reep 1, Ghent 9000, Belgium.,Pharmaceutical Care & Pharmaco-economics, KU Leuven, O&N II, Leuven 3001, Belgium
| | - Smita Rawal
- Department of Pharmaceutical Health Services, Outcomes & Policy, College of Pharmacy, University of Georgia, Athens 30602, GA, USA
| | - Walter Van Dyck
- Healthcare Management Centre, Vlerick Business School, Reep 1, Ghent 9000, Belgium.,Pharmaceutical Care & Pharmaco-economics, KU Leuven, O&N II, Leuven 3001, Belgium
| | - Isabelle Huys
- Pharmaceutical Care & Pharmaco-economics, KU Leuven, O&N II, Leuven 3001, Belgium
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48
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Ribociclib in hormone-receptor-positive advanced breast cancer: Establishing a value-based cost in China. Breast 2018; 43:1-6. [PMID: 30342258 DOI: 10.1016/j.breast.2018.10.004] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2018] [Revised: 09/28/2018] [Accepted: 10/15/2018] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND The addition of ribociclib (RIB) to letrozole (LET) significantly increases progression free survival for patients with hormone-receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC). We identified the range of drug costs for which RIB could be considered cost effective from a Chinese perspective. METHODS A discrete event simulation model was developed to model the treatment sequences among patients with ABC. Life years (LYs), quality-adjusted LYs (QALYs) and lifetime costs were estimated. Costs were estimated for Chinese health care systems. Three times the per capita gross domestic product (GDP) of China 2016 ($24,360) and three times the per capita GDP of Beijing city 2016 ($53,384) were used as the willingness-to-pay threshold. Probabilistic sensitivity analyses were performed. RESULTS In the base case analysis, RIB + LET provided an incremental survival benefit of 0.631 LYs and 0.451 QALYs. When RIB costs less than $721 or $1170 per 4 weeks, there was a nearly 90% likelihood that the incremental cost-effectiveness ratio for RIB + LET would be less than $24,360 per QALY or $53,384 per QALY, respectively. CONCLUSION A value-based price for the cost of RIB is $732 or $1170 per 4 weeks for China and Beijing City, respectively. Our study is helpful to inform the multilateral drug price negotiations in China that may be upcoming for RIB.
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Dickkopf-1 (Dkk1) protein expression in breast cancer with special reference to bone metastases. Clin Exp Metastasis 2018; 35:763-775. [PMID: 30238177 DOI: 10.1007/s10585-018-9937-3] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2018] [Accepted: 09/18/2018] [Indexed: 12/15/2022]
Abstract
Dysregulation of the Wnt inhibitor dickkopf-1 protein (Dkk1) has been reported in a variety of cancers. In addition, it has been linked to the progression of malignant bone disease by impairing osteoblast activity. This study investigated serum- and tissue levels of Dkk1 in breast cancer patients with- or without bone metastases. Serum Dkk1 levels were measured by ELISA in 89 breast cancer patients and 86 healthy women. Tissue levels of Dkk1 and β-catenin, a major downstream component of Wnt transduction pathway, were tested with immunohistochemical staining in 143 different tissues, including adjacent non-tumoral breast tissues, primary breast tumours, lymph nodes metastases, and bone metastases. Serum levels of Dkk1 were significantly increased in breast cancer patients without metastases compared with healthy controls and even more increased in patients with bone metastases. Tissue expression of Dkk1 was positive in 70% of tested primary breast cancer tissues and demonstrated significant correlation with histological type and PR status. Less frequent expression of Dkk1 was found in lymph nodes metastases and bone metastases compared with adjacent non-tumoral breast tissues and primary breast tumours. Tissue expression of β-catenin was positive in the vast majority of all tested tissue types indicating activated Wnt/β-catenin signalling. Our results suggested that Wnt/β-catenin signalling in breast tumours and their secondary lymph nodes- and bone metastases is dysregulated and this could be related to aberrant Dkk1 expression levels. Hence, Dkk1 protein might provide insights into the continued development of novel comprehensive and therapeutic strategies for breast cancer and its bone metastases.
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50
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Qian Y, Maruyama S, Kim H, Pollom EL, Kumar KA, Chin AL, Harris JP, Chang DT, Pitt A, Bendavid E, Owens DK, Durkee BY, Soltys SG. Cost-effectiveness of radiation and chemotherapy for high-risk low-grade glioma. Neuro Oncol 2018; 19:1651-1660. [PMID: 28666368 DOI: 10.1093/neuonc/nox121] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Background The addition of procarbazine, lomustine, vincristine (PCV) chemotherapy to radiotherapy (RT) for patients with high-risk (≥40 y old or subtotally resected) low-grade glioma (LGG) results in an absolute median survival benefit of over 5 years. We evaluated the cost-effectiveness of this treatment strategy. Methods A decision tree with an integrated 3-state Markov model was created to follow patients with high-risk LGG after surgery treated with RT versus RT+PCV. Patients existed in one of 3 health states: stable, progressive, or dead. Survival and freedom from progression were modeled to reflect the results of RTOG 9802 using time-dependent transition probabilities. Health utility values and costs of care were derived from the literature and national registry databases. Analysis was conducted from the health care perspective. Deterministic and probabilistic sensitivity analysis explored uncertainty in model parameters. Results Modeled outcomes demonstrated agreement with clinical data in expected benefit of addition of PCV to RT. The addition of PCV to RT yielded an incremental benefit of 4.77 quality-adjusted life-years (QALYs) (9.94 for RT+PCV vs 5.17 for RT alone) at an incremental cost of $48635 ($188234 for RT+PCV vs $139598 for RT alone), resulting in an incremental cost-effectiveness ratio of $10186 per QALY gained. Probabilistic sensitivity analysis demonstrates that within modeled distributions of parameters, RT+PCV has 99.96% probability of being cost-effectiveness at a willingness-to-pay threshold of $100000 per QALY. Conclusion The addition of PCV to RT is a cost-effective treatment strategy for patients with high-risk LGG.
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Affiliation(s)
- Yushen Qian
- Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California; Department of Health Research and Policy, Stanford University, Stanford, California; Division of Management Science and Engineering, Department of Engineering, Stanford University, Stanford, California; VA Palo Alto Health Care System, and Center for Primary Care and Outcomes Research/Center for Health Policy, Department of Medicine, Stanford University, Stanford, California; Swedish American Hospital, a division of the University of Wisconsin, Rockford, Illinois
| | - Satoshi Maruyama
- Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California; Department of Health Research and Policy, Stanford University, Stanford, California; Division of Management Science and Engineering, Department of Engineering, Stanford University, Stanford, California; VA Palo Alto Health Care System, and Center for Primary Care and Outcomes Research/Center for Health Policy, Department of Medicine, Stanford University, Stanford, California; Swedish American Hospital, a division of the University of Wisconsin, Rockford, Illinois
| | - Haju Kim
- Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California; Department of Health Research and Policy, Stanford University, Stanford, California; Division of Management Science and Engineering, Department of Engineering, Stanford University, Stanford, California; VA Palo Alto Health Care System, and Center for Primary Care and Outcomes Research/Center for Health Policy, Department of Medicine, Stanford University, Stanford, California; Swedish American Hospital, a division of the University of Wisconsin, Rockford, Illinois
| | - Erqi L Pollom
- Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California; Department of Health Research and Policy, Stanford University, Stanford, California; Division of Management Science and Engineering, Department of Engineering, Stanford University, Stanford, California; VA Palo Alto Health Care System, and Center for Primary Care and Outcomes Research/Center for Health Policy, Department of Medicine, Stanford University, Stanford, California; Swedish American Hospital, a division of the University of Wisconsin, Rockford, Illinois
| | - Kiran A Kumar
- Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California; Department of Health Research and Policy, Stanford University, Stanford, California; Division of Management Science and Engineering, Department of Engineering, Stanford University, Stanford, California; VA Palo Alto Health Care System, and Center for Primary Care and Outcomes Research/Center for Health Policy, Department of Medicine, Stanford University, Stanford, California; Swedish American Hospital, a division of the University of Wisconsin, Rockford, Illinois
| | - Alexander L Chin
- Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California; Department of Health Research and Policy, Stanford University, Stanford, California; Division of Management Science and Engineering, Department of Engineering, Stanford University, Stanford, California; VA Palo Alto Health Care System, and Center for Primary Care and Outcomes Research/Center for Health Policy, Department of Medicine, Stanford University, Stanford, California; Swedish American Hospital, a division of the University of Wisconsin, Rockford, Illinois
| | - Jeremy P Harris
- Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California; Department of Health Research and Policy, Stanford University, Stanford, California; Division of Management Science and Engineering, Department of Engineering, Stanford University, Stanford, California; VA Palo Alto Health Care System, and Center for Primary Care and Outcomes Research/Center for Health Policy, Department of Medicine, Stanford University, Stanford, California; Swedish American Hospital, a division of the University of Wisconsin, Rockford, Illinois
| | - Daniel T Chang
- Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California; Department of Health Research and Policy, Stanford University, Stanford, California; Division of Management Science and Engineering, Department of Engineering, Stanford University, Stanford, California; VA Palo Alto Health Care System, and Center for Primary Care and Outcomes Research/Center for Health Policy, Department of Medicine, Stanford University, Stanford, California; Swedish American Hospital, a division of the University of Wisconsin, Rockford, Illinois
| | - Allison Pitt
- Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California; Department of Health Research and Policy, Stanford University, Stanford, California; Division of Management Science and Engineering, Department of Engineering, Stanford University, Stanford, California; VA Palo Alto Health Care System, and Center for Primary Care and Outcomes Research/Center for Health Policy, Department of Medicine, Stanford University, Stanford, California; Swedish American Hospital, a division of the University of Wisconsin, Rockford, Illinois
| | - Eran Bendavid
- Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California; Department of Health Research and Policy, Stanford University, Stanford, California; Division of Management Science and Engineering, Department of Engineering, Stanford University, Stanford, California; VA Palo Alto Health Care System, and Center for Primary Care and Outcomes Research/Center for Health Policy, Department of Medicine, Stanford University, Stanford, California; Swedish American Hospital, a division of the University of Wisconsin, Rockford, Illinois
| | - Douglas K Owens
- Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California; Department of Health Research and Policy, Stanford University, Stanford, California; Division of Management Science and Engineering, Department of Engineering, Stanford University, Stanford, California; VA Palo Alto Health Care System, and Center for Primary Care and Outcomes Research/Center for Health Policy, Department of Medicine, Stanford University, Stanford, California; Swedish American Hospital, a division of the University of Wisconsin, Rockford, Illinois
| | - Ben Y Durkee
- Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California; Department of Health Research and Policy, Stanford University, Stanford, California; Division of Management Science and Engineering, Department of Engineering, Stanford University, Stanford, California; VA Palo Alto Health Care System, and Center for Primary Care and Outcomes Research/Center for Health Policy, Department of Medicine, Stanford University, Stanford, California; Swedish American Hospital, a division of the University of Wisconsin, Rockford, Illinois
| | - Scott G Soltys
- Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California; Department of Health Research and Policy, Stanford University, Stanford, California; Division of Management Science and Engineering, Department of Engineering, Stanford University, Stanford, California; VA Palo Alto Health Care System, and Center for Primary Care and Outcomes Research/Center for Health Policy, Department of Medicine, Stanford University, Stanford, California; Swedish American Hospital, a division of the University of Wisconsin, Rockford, Illinois
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