Background: For 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.
Methods: We 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).
Results: We 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 = 0.28, 95% CrI=0.23 to 0.34), enzalutamide (HR = 0.30, 95% CrI=0.25 to 0.36), darolutamide (HR = 0.41, 95% CrI=0.34 to 0.49); darolutamide led to the lowest hazard of death (HR = 0.69, 95% CrI= 0.53 to 0.90), followed by enzalutamide (HR = 0.73, 95% CrI=0.61 to 0.87) and apalutamide (HR = 0.75, 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 = 1.43, 95% CrI=1.08 to 1.89), apalutamide (OR = 1.58, 95% CrI=1.23 to 2.03), and abiraterone acetate (OR = 1.94, 95% CrI=1.17 to 3.22).
Conclusions: For 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.
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