Cost-Effectiveness of Second-Line Endocrine Therapies in Postmenopausal Women with Hormone Receptor–positive and Human Epidermal Growth Factor Receptor 2–negative Metastatic Breast Cancer in Japan
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Exemestane (EXE), exemestane + everolimus (EXE + EVE), toremifene (TOR), and fulvestrant (FUL) are second-line endocrine therapies for postmenopausal hormone receptor–positive (HR +)/human epidermal growth factor receptor 2–negative (HER2 −) metastatic breast cancer (mBC) in Japan. Although the efficacy of these therapies has been shown in recent studies, cost-effectiveness has not yet been determined in Japan.
This study aimed to examine the cost-effectiveness of second-line endocrine therapies for the treatment of postmenopausal women with HR + and HER2 − mBC.
A Markov model was developed to analyze the cost-effectiveness of the therapies over a 15-year time horizon from a public healthcare payer’s perspective. The efficacy and utility parameters were determined via a systematic search of the literature. Direct medical care costs were used. A discount rate of 2% was applied for costs and outcomes. Subgroup analysis was performed for non-visceral metastasis. A series of sensitivity analyses, including probabilistic sensitivity analysis (PSA) and threshold analysis were performed.
Base-case analyses estimated incremental cost-effectiveness ratios (ICERs) of 3 million and 6 million Japanese yen (JPY)/quality-adjusted life year (QALY) gained for TOR and FUL 500 mg relative to EXE, respectively. FUL 250 mg and EXE + EVE were dominated. The overall survival (OS) highly influenced the ICER. With a willingness-to-pay (WTP) threshold of 5 million JPY/QALY, the probability of TOR being cost-effective was the highest. Subgroup analysis in non-visceral metastasis revealed 0.4 and 10% reduction in ICER from the base-case results of FUL5 500 mg versus EXE and TOR versus EXE, respectively, while threshold analysis indicated EVE and FUL prices should be reduced 73 and 30%, respectively.
As a second-line therapy for postmenopausal women with HR +/HER2 − mBC, TOR may be cost-effective relative to other alternatives and seems to be the most favorable choice, based on a WTP threshold of 5 million JPY/QALY. FUL 250 mg is expected to be as costly and effective as EXE. The cost-effectiveness of EXE + EVE and FUL 500 mg could be improved by a large price reduction. However, the results are highly sensitive to the hazard ratio of OS. Policy makers should carefully interpret and utilize these findings.
The authors would like to thank Rosarin Sruamsiri, a former staff member at the Center of Pharmaceutical Outcomes Research, Naresuan University, Thailand, for providing technical guidance regarding economic evaluation model development, and Takeru Shiroiwa, Senior researcher at the Department of Health and Welfare Services, National Institute of Public Health, for his review and comments on the methodology of this study. The model used in this study was provided to the journal’s peer reviewers for their reference when reviewing the manuscript. Verin Lertjanyakun was supported by the 2017 Kyoto University School of Public Health—Super Global Course’s travel scholarship to Naresuan University, Phitsanulok, Thailand through the Top Global University Project “Japan Gateway: Kyoto University Top Global Program,” sponsored by the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan. This study was supported by a JSPS Grant-in-Aid Scientific Research (A) (16H02634).
VL participated in the design of the study, developed the cost-effectiveness model, conducted the expert meetings, searched input parameters, conducted the cost-effectiveness analyses, and drafted the manuscript. NC and YI participated in the design of the study, developed the cost-effectiveness models, and drafted the manuscript. KS participated in the design of the study and searched input parameters. Each author also contributed to the interpretation of data and results, critically reviewing the manuscript for important issues, and has approved the final version.
Compliance with Ethical Standards
Conflicts of interest
V.L., N.C., S.W., and Y.I. declare that they have no conflicts of interest. No sponsors were involved in this study.
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