201 Background: Metastatic castration resistant prostate cancer remains a lethal stage despite major therapeutic advances. The introduction of androgen receptor targeted agents and PARP inhibitors has redefined first line management. However, the optimal regimen and relative efficacy among available therapies remain uncertain, as pivotal trials were conducted in distinct populations and lacked direct comparative data. Methods: A Bayesian network meta analysis was performed using data from four phase III randomized trials: PROpel, COU AA 302, ACIS, and PREVAIL, including 8997 patients. Hazard ratios for radiographic progression free survival and overall survival were extracted. Relative treatment effects were estimated using a Bayesian hierarchical model integrating direct and indirect head to head comparisons. Surface Under the Cumulative Ranking (SUCRA) probabilities were derived to rank each regimen by likelihood of being most effective. Results: Among 8997 patients from four phase III trials, Olaparib plus Abiraterone ranked highest for progression free survival, while Abiraterone showed the greatest overall survival probability. Enzalutamide provided consistent efficacy across both endpoints. SUCRA based ranking as mentioned in the table 1 showed clear separation between treatment and control arms. Conclusions: This network meta analysis defines the first unified hierarchy of first line regimens for metastatic castration resistant prostate cancer, integrating nearly nine thousand patients from pivotal trials. Olaparib plus Abiraterone achieved the greatest delay in progression, reinforcing the synergistic potential of PARP inhibition with androgen receptor blockade. Abiraterone showed the highest overall survival probability, confirming its position as the most validated survival benchmark, while Enzalutamide maintained consistent efficacy across both endpoints. Overall survival data for PARP inhibitor combinations remain premature but suggest meaningful benefit with longer follow up. These findings define a clear evidence based hierarchy of efficacy, guiding regimen selection when toxicity, cost, or access limit preferred agents, and highlight the evolution of mCRPC therapy toward mechanism driven combinations that extend survival and quality of life. Rank Treatment SUCRA (95% CrI) rPFS SUCRA (95% CrI) OS 1 Olaparib + Abiraterone + Prednisone 92 (85–98) 82 (70–93) 2 Abiraterone + Prednisone 78 (65–89) 85 (75–94) 3 Enzalutamide 65 (52–78) 80 (68–91) 4 Apalutamide + Abiraterone 45 (32–58) 38 (25–51) 5–6 Placebo ± Prednisone 15 (5–25) / 5 (1–12) ≤ 15 Ranking based on Bayesion head to head analysis and SUCRA scores of rPFS (radiological progression free interval) and OS (overall survival).
Patel et al. (Sun,) studied this question.