Verin Lertjanyakun1, Nathorn Chaiyakunapruk2,3,4,5, Susumu Kunisawa1, Yuichi Imanaka6. 1. Department of Healthcare Economics and Quality Management, Graduate School of Medicine, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto, 606-8501, Japan. 2. School of Pharmacy, Monash University Malaysia, Subang Jaya, Selangor, Malaysia. 3. Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Center of Pharmaceutical Outcomes Research, Naresuan University, Phitsanulok, Thailand. 4. School of Pharmacy, University of Wisconsin-Madison, Wisconsin, USA. 5. Asian Centre for Evidence Synthesis in Population, Implementation and Clinical Outcomes, Health and Well-being Cluster, Global Asia in the 21st Century (GA21) Platform, Monash University Malaysia, Subang Jaya, Selangor, Malaysia. 6. Department of Healthcare Economics and Quality Management, Graduate School of Medicine, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto, 606-8501, Japan. imanaka-y@umin.net.
Abstract
BACKGROUND: 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. OBJECTIVE: This study aimed to examine the cost-effectiveness of second-line endocrine therapies for the treatment of postmenopausal women with HR + and HER2 - mBC. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
BACKGROUND: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. OBJECTIVE: This study aimed to examine the cost-effectiveness of second-line endocrine therapies for the treatment of postmenopausal women with HR + and HER2 - mBC. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Authors: José Baselga; Mario Campone; Martine Piccart; Howard A Burris; Hope S Rugo; Tarek Sahmoud; Shinzaburo Noguchi; Michael Gnant; Kathleen I Pritchard; Fabienne Lebrun; J Thaddeus Beck; Yoshinori Ito; Denise Yardley; Ines Deleu; Alejandra Perez; Thomas Bachelot; Luc Vittori; Zhiying Xu; Pabak Mukhopadhyay; David Lebwohl; Gabriel N Hortobagyi Journal: N Engl J Med Date: 2011-12-07 Impact factor: 91.245
Authors: Andrew H Briggs; Milton C Weinstein; Elisabeth A L Fenwick; Jonathan Karnon; Mark J Sculpher; A David Paltiel Journal: Med Decis Making Date: 2012 Sep-Oct Impact factor: 2.583
Authors: H Yamashita; H Iwase; T Toyama; S Takahashi; H Sugiura; N Yoshimoto; Y Endo; Y Fujii; S Kobayashi Journal: Ann Oncol Date: 2010-11-30 Impact factor: 32.976
Authors: Dorothy A White; Philippe Camus; Masahiro Endo; Bernard Escudier; Emiliano Calvo; Hideyuki Akaza; Hirotsugu Uemura; Euloge Kpamegan; Andrea Kay; Matthew Robson; Alain Ravaud; Robert J Motzer Journal: Am J Respir Crit Care Med Date: 2010-03-01 Impact factor: 21.405
Authors: Denise A Yardley; Shinzaburo Noguchi; Kathleen I Pritchard; Howard A Burris; José Baselga; Michael Gnant; Gabriel N Hortobagyi; Mario Campone; Barbara Pistilli; Martine Piccart; Bohuslav Melichar; Katarina Petrakova; Francis P Arena; Frans Erdkamp; Wael A Harb; Wentao Feng; Ayelet Cahana; Tetiana Taran; David Lebwohl; Hope S Rugo Journal: Adv Ther Date: 2013-10-25 Impact factor: 3.845
Authors: F Cardoso; A Costa; E Senkus; M Aapro; F André; C H Barrios; J Bergh; G Bhattacharyya; L Biganzoli; M J Cardoso; L Carey; D Corneliussen-James; G Curigliano; V Dieras; N El Saghir; A Eniu; L Fallowfield; D Fenech; P Francis; K Gelmon; A Gennari; N Harbeck; C Hudis; B Kaufman; I Krop; M Mayer; H Meijer; S Mertz; S Ohno; O Pagani; E Papadopoulos; F Peccatori; F Penault-Llorca; M J Piccart; J Y Pierga; H Rugo; L Shockney; G Sledge; S Swain; C Thomssen; A Tutt; D Vorobiof; B Xu; L Norton; E Winer Journal: Ann Oncol Date: 2017-01-01 Impact factor: 32.976