This study was designed to evaluate the efficacy, tolerability, and sequential administration of abiraterone acetate (AA) and enzalutamide (Enz) for metastatic castration-resistant prostate cancer (mCRPC). A literature search was performed with PubMed, Embase, and Web of Science databases to identify relevant studies. Reviewed literature included published phase III trials of AA or Enz in mCRPC and studies regarding their sequential administration. Given the difference in control arms in AA (active comparator) and Enz (true placebo) randomized phase III studies, indirect comparisons between AA and Enz in mCRPC showed no statistically significant difference in overall survival in prechemotherapy and postchemotherapy settings (HR: 0.90, 95% CI, 0.73-1.11; HR: 0.85, 95% CI, 0.68-1.07). Compared with AA, Enz may better outperform control arms in treating mCRPC both before and after chemotherapy regarding secondary endpoints based on indirect comparisons: time to prostate-specific antigen (PSA) progression (HR: 0.34, 95% CI, 0.28-0.42; HR: 0.40, 95% CI, 0.30-0.53), radiographic progression-free survival (HR: 0.37, 95% CI, 0.28-0.48; HR: 0.61, 95% CI, 0.50-0.74), and PSA response rate (OR: 18.29, 95% CI, 11.20-29.88; OR: 10.69, 95% CI, 3.92-29.20). With regard to the effectiveness of Enz following AA or AA following Enz, recent retrospective case series reported overall survival and secondary endpoints for patients with mCRPC progression after chemotherapy. However, confirmatory head-to-head trials are necessary to determine the optimal sequencing of these agents.

Keywords: abiraterone acetate; enzalutamide; indirect comparison; metastatic castration-resistant prostate cancer; sequential therapy

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