Authors' objectives: The Academic Technology Assessment Group (ATAG) reviewed a report by the manufacturer (Astra-Zeneca K.K.) of capivasertib for hormone receptor-positive, HER2-negative unresectable, or recurrent breast cancer with PIK3CA, AKT1, or PTEN alterations following endocrine therapy progression. The intervention was capivasertib plus fulvestrant, with fulvestrant plus a CDK4/6 inhibitor (switch) as the base-case comparator and exemestane plus everolimus for scenario analysis. As no randomised controlled trials (RCTs) have directly compared capivasertib with comparators, the manufacturer conducted a network meta-analysis (NMA). For progression-free survival (PFS), the NMA using 10 trials estimated a hazard ratio (HR) of 0.53 (95% confidence interval [CI]: 0.33-0.85) for capivasertib plus fulvestrant versus fulvestrant plus abemaciclib, demonstrating statistically significant PFS prolongation. For overall survival (OS), the NMA using 5 trials estimated an HR of 0.78 (95% CI: 0.43- 1.43) versus fulvestrant plus palbociclib, showing no statistically significant difference. The manufacturer concluded that capivasertib had additional benefits. The ATAG independently conducted a systematic review and identified four trials: CAPItello-291, postMONARCH, PACE, and MAINTAIN. For the base-case analysis, ATAG excluded PACE and MAINTAIN, which evaluated CDK4/6 inhibitor continuation, and performed an indirect comparison using postMONARCH, which assessed the switch strategy. The analysis yielded an HR of 0.53 (95% CI: 0.33- 0.86) for PFS, demonstrating a statistically significant improvement. As OS data were immature in post- MONARCH, the ATAG did not use OS to determine additional benefits. The ATAG concluded that capivasertib plus fulvestrant demonstrated additional benefits compared to fulvestrant plus abemaciclib. In the scenario analysis, additional benefits were also demonstrated for exemestane plus everolimus. In the cost-effectiveness analysis, the manufacturer employed a partitioned survival model comprising three health states-progression-free, post-progression, and death. The ATAG conducted a reanalysis owing to the several challenges identified in the analysis by the manufacturer. In the ATAG reanalysis, given that the postMONARCH trial demonstrated a statistically significant improvement in PFS for fulvestrant plus abemaciclib compared with fulvestrant monotherapy, a corresponding benefit in OS was inferred. To address the uncertainty surrounding OS estimates, the ATAG conducted sensitivity analyses in which the OS hazard ratio for fulvestrant plus abemaciclib versus fulvestrant monotherapy was varied between 0.85 and 1.02, supplementing the base-case analysis that assumed a hazard ratio of 0.95. Furthermore, the ATAG applied the most recent drug prices and excluded the cost of genetic testing from the analysis. The base-case analysis showed that compared to fulvestrant plus abemaciclib, capivasertib plus fulvestrant resulted in incremental costs of JPY 8,937,592 and incremental effects of 0.64 quality-adjusted life years (QALYs), yielding an incremental cost-effectiveness ratio (ICER) of JPY 13,994,792/QALY. From the perspective of public healthcare in Japan, the ICER for capivasertib plus fulvestrant is likely to fall within the range of \11.25 million/QALY or more but less than \15 million/ QALY in the base case analysis.

Project Status: Completed

URL for project: https://c2h.niph.go.jp/en/

Year Published: 2025

URL for published report: https://c2h.niph.go.jp/en/results/C2H2402.html

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: Japan

Organisation Name: Center for Outcomes Research and Economic Evaluation for Health

Contact Address: 2-3-6 Minami, Wako-shi, Saitama 351-0197 Japan

Contact Name: Takeru Shiroiwa

Contact Email: t.shiroiwa@gmail.com