Comparative efficacy and safety of novel androgen receptor inhibitors in nonmetastatic castration-resistant prostate cancer: A systematic review and Bayesian network meta-analysis.

Abstract

e17042 Background: Nonmetastatic castration-resistant prostate cancer (nmCRPC) progresses despite androgen deprivation therapy (ADT), necessitating additional therapeutic strategies. Novel non-steroidal anti-androgens (NSAAs), including enzalutamide, apalutamide, and darolutamide, have demonstrated improved metastasis-free survival (MFS) and overall survival (OS) when combined with ADT compared to ADT alone. However, direct head-to-head comparisons among these agents are limited, complicating treatment selection. This study employs a Bayesian network meta-analysis (NMA) to compare the efficacy and safety of NSAAs combined with ADT, providing clinicians with an evidence-based ranking of treatment options for nmCRPC. Methods: A Bayesian NMA was conducted using data from 10 randomized controlled trials (RCTs) encompassing 7,429 patients with nmCRPC. The comparative efficacy and safety of apalutamide, enzalutamide, and darolutamide in combination with ADT were assessed using mean differences (MDs) with 95% credible intervals (CrIs) for key outcomes, including OS, progression-free survival (PFS), MFS, and time to prostate-specific antigen progression (TTPP). Treatment rankings were determined using Surface Under the Cumulative Ranking Curve (SUCRA) values. Results: In this analysis, apalutamide demonstrated the highest efficacy for overall survival (OS) (SUCRA: 75.7%, MD: 42.99 months, 95% CrI: -18.78 to 104.82), followed by darolutamide (SUCRA: 62.53%) and enzalutamide (SUCRA: 42.67%). For progression-free survival (PFS), darolutamide ranked highest (SUCRA: 76.22%, MD: 21.99 months, 95% CrI: -6.51 to 50.43), followed by apalutamide (SUCRA: 70.6%). Enzalutamide showed the greatest efficacy for metastasis-free survival (MFS) (SUCRA: 84.22%, MD: 57.28 months, 95% CrI: -0.36 to 114.86), followed by darolutamide (SUCRA: 73.45%). For time to prostate-specific antigen progression (TTPP), apalutamide ranked highest (SUCRA: 69.93%, MD: 57.92 months, 95% CrI: -39.94 to 155.68), followed by enzalutamide (SUCRA: 62.77%). These findings suggest that novel androgen receptor inhibitors, particularly apalutamide and darolutamide, significantly improve outcomes in nmCRPC. Conclusions: This study provides a comparative assessment of NSAAs in nmCRPC, highlighting their variable efficacy across different survival outcomes. Apalutamide demonstrated the greatest benefit in OS and TTPP, while darolutamide was most effective for PFS. Enzalutamide showed superior efficacy in improving MFS. All three NSAAs significantly outperformed ADT alone, underscoring their role in nmCRPC management. These findings offer critical insights into the relative benefits of NSAAs, aiding clinicians in personalized treatment selection for nmCRPC patients.