Comparison of Treatments for Nonmetastatic Castration-Resistant Prostate Cancer: Matching-Adjusted Indirect Comparison and Network Meta-Analysis.

Abstract

BACKGROUND\nFor nonmetastatic castration-resistant prostate cancer (nmCRPC), three drugs under patent protection-apalutamide, enzalutamide, and darolutamide-were approved based on randomized, placebo-controlled trials; one drug with generic availability-abiraterone acetate-showed efficacy in a single-arm trial and is commonly prescribed. Lacking head-to-head trials, the optimal treatment for nmCRPC is unknown, despite widely varied treatment costs. We compared the efficacy and safety of nmCRPC treatments.\n\n\nMETHODS\nWe searched bibliographic databases, regulatory documents, and trial registries for nmCRPC trials. We included published results and, when available original data. We performed matching-adjusted indirect comparison and network meta-analysis and compared treatments regarding metastasis-free survival (MFS), overall survival (OS), and serious adverse events (SAE).\n\n\nRESULTS\nWe analyzed five trials with a total of 4,360 participants. Compared with placebo, abiraterone acetate engendered the lowest hazard of metastasis/death (hazard ratio [HR] = 0.22, 95% credible interval [CrI] = 0.12 to 0.41), followed by apalutamide (HR\u2009=\u20090.28, 95% CrI=0.23 to 0.34), enzalutamide (HR\u2009=\u20090.30, 95% CrI=0.25 to 0.36), darolutamide (HR\u2009=\u20090.41, 95% CrI=0.34 to 0.49); darolutamide led to the lowest hazard of death (HR\u2009=\u20090.69, 95% CrI= 0.53 to 0.90), followed by enzalutamide (HR\u2009=\u20090.73, 95% CrI=0.61 to 0.87) and apalutamide (HR\u2009=\u20090.75, 95% CrI=0.59 to 0.95); darolutamide resulted in the lowest odds of SAEs (odds ratio [OR] = 1.32, 95% CrI= 1.02 to 1.70), followed by enzalutamide (OR\u2009=\u20091.43, 95% CrI=1.08 to 1.89), apalutamide (OR\u2009=\u20091.58, 95% CrI=1.23 to 2.03), and abiraterone acetate (OR\u2009=\u20091.94, 95% CrI=1.17 to 3.22).\n\n\nCONCLUSIONS\nFor nmCRPC, darolutamide offered optimal efficacy and safety among approved drugs, abiraterone acetate may offer comparable MFS benefit with cost-savings from generic availability. Future research is needed to more fully examine abiraterone acetate s benefit.