Review of second-generation androgen receptor inhibitor therapies and their role in prostate cancer management.

PURPOSE OF REVIEW: We review the published literature on the indications of second-generation androgen receptor inhibitors, Poly(ADP-Ribose) Polymerase (PARP) inhibitors, combination therapies, and their evolution throughout the advanced prostate cancer continuum. RECENT FINDINGS: Enzalutamide trials have published data supporting its use in metastatic hormone-sensitive prostate cancer (mHSPC), nonmetastatic castration-resistant prostate cancer (nmCRPC), and metastatic castration-resistant prostate cancer (mCRPC). Apalutamide trials have supported its indication for mHSPC and nmCRPC. Darolutamide trials currently support its use for nmCRPC. Abiraterone trials have supported its use in mCRPC and mHSPC. Olaparib and rucaparib have shown clinical benefit in heavily pretreated patients with mCRPC and DNA repair mutation genes. SUMMARY: Phase 3 trials and peer-reviewed literature demonstrate that enzalutamide, apalutamide, and darolutamide prolong overall survival (OS) in men with nmCRPC. Abiraterone, enzalutamide, and apalutamide improve OS in men with mHSPC. Abiraterone and enzalutamide have data supporting improvement in OS in men with mCRPC.