Comparison of Oncologic Outcomes between Two Alternative Sequences with Abiraterone Acetate and Enzalutamide in Patients with Metastatic Castration-Resistant Prostate Cancer: A Systematic Review and Meta-Analysis

Sequential treatment of androgen receptor axis targeted agents (ARAT), abiraterone acetate (ABI) and enzalutamide (ENZA), in metastatic castration-resistant prostate cancer (mCRPC) demonstrated some positive effects, but cross-resistances between ABI and ENZA that reduce activity have been suggested. Therefore, we conducted a meta-analysis to compare oncologic outcomes between the treatment sequences of ABI-ENZA and ENZA-ABI in patients with mCRPC. The primary endpoint was a combined progression-free survival (PFS), and the secondary endpoint was overall survival (OS). A total of five trials on 553 patients were included in this study. Each of the included studies was retrospective. In two studies including both chemo-naive and post-chemotherapy mCRPC patients, for ABI-ENZA compared with ENZA-ABI, pooled hazard ratios (HRs) for PFS and OS were 0.37 (p < 0.0001; 95% confidence intervals (CIs), 0.23-0.60) and 0.64 (p = 0.10; 95% CIs, 0.37-1.10), respectively. In three studies with chemo-naive mCRPC patients only, for ABI-ENZA compared with ENZA-ABI, pooled HRs for PFS and OS were 0.57 (p = 0.02; 95% CIs, 0.35-0.92) and 0.86 (p = 0.39; 95% CIs, 0.61-1.21), respectively. The current meta-analysis revealed that ABI-ENZA had a significantly more favorable oncological outcome, but the level of evidence was low. Therefore, large-scale randomized trials may be needed.