Efficacy and Safety Differences Between Abiraterone and Enzalutamide in Patients with Metastatic Castration-Resistant Prostate Cancer: A Systematic Review and Meta-analysis of Real-World Studies

BACKGROUND: Abiraterone (ABI) and enzalutamide (ENZA) are standard treatments for metastatic castration-resistant prostate cancer (mCRPC). However, their safety and efficacy have not been directly compared in prospective clinical trials. OBJECTIVE: To directly compare their safety and efficacy in prospective clinical trials. PATIENTS AND METHODS: A systematic search was performed in PubMed, Embase, and Cochrane Library databases (CRD42024608496) on 24 June 2025. Eligibility criteria included studies on patients with mCRPC treated with ABI or ENZA reporting outcomes such as overall survival (OS), prostate-specific antigen (PSA) response (PSA50/90), progression-free survival (rPFS/bPFS), and rates of grade ≥ 3 adverse events, dose reduction, treatment discontinuation, and major cardiovascular events (MACE). Both first- and second-line mCRPC treatment settings were considered. The inverse variance method was used to calculate pooled hazard ratios (HRs), using the natural logarithm of the HR and its standard error (SE) from the available data. RESULTS: A total of 47 real-world observation studies and data from 71,984 patients were included, with no randomized controlled trials available for direct comparison. ENZA proved more effective in terms of PSA50 (odds ratio (OR): 1.82; 95% confidence interval (CI): 1.38-2.4) and OS (HR: 0.79; 95% CI 0.71-0.87) in the overall cohort as well as in the first-line (PSA50: OR: 1.69; 95% CI 1.23-2.31, OS: HR: 0.85, 95% CI 0.79-0.92) and second-line setting (PSA50 OR: 1.78; 95% CI 1.23-2.58, OS: HR: 0.69; 95% CI 0.60-0.80). However, grade ≥ 3 AEs and treatment discontinuation rates were significantly more frequent with ENZA (OR: 2.17; 95% CI 0.85-5.54 and OR: 1.81; 95% CI 1.45-2.25, respectively), while MACE rates were lower (OR: 0.53; 95% CI 0.33-0.84). CONCLUSIONS: ENZA showed greater efficacy, whereas serious AEs were less frequent with ABI. However, this difference may decrease or even disappear upon switching these therapies. Therefore, individual decision-making is encouraged, balancing efficacy and safety. ENZA should be prioritized if OS is the main goal, whereas ABI may be preferred when minimizing AEs is important. ENZA is also associated with a lower risk of MACE.