Comparative effectiveness of androgen receptor pathway inhibitor treatment intensification for metastatic hormone-sensitive prostate cancer in real-world patients.

PURPOSE: This study compared the real-world effectiveness of androgen receptor pathway inhibitors (ARPIs)-abiraterone acetate, apalutamide, and enzalutamide-as treatment intensification in patients with metastatic hormone-sensitive prostate cancer (mHSPC). MATERIALS AND METHODS: This multicenter retrospective cohort study analyzed 219 patients with mHSPC who received first-line ARPIs combined with androgen deprivation therapy. We evaluated progression-free survival to metastatic castration-resistant prostate cancer (PFS to mCRPC) and prostate-specific antigen (PSA) response within 12 weeks and investigated the prognostic impact of early PSA response on clinical outcomes. RESULTS: The cohort comprised patients receiving abiraterone acetate (n=94, 42.9%), apalutamide (n=91, 41.6%), and enzalutamide (n=34, 15.5%) with an 18.8-month median follow-up. The 2-year PFS to mCRPC rates demonstrated no significant difference between the groups (abiraterone acetate: 74.1%; apalutamide, 81.4%; enzalutamide, 85.6%; p=0.482). However, apalutamide and enzalutamide achieved superior rates of PSA decline to ≤0.2 ng/mL within 12 weeks compared with abiraterone acetate (44.0% and 55.9% vs. 25.5%, respectively) and significantly shorter median time to PSA nadir (7.2 and 7.5 months vs. 12.2 months; p<0.001). A PSA reduction of ≥90% within 12 weeks was observed in 87.2%, 94.5%, and 97.1% of patients receiving abiraterone acetate, apalutamide, and enzalutamide, respectively. Multivariate analysis identified early PSA response as an independent prognostic factor for improved PFS to mCRPC regardless of ARPI selection. CONCLUSIONS: Abiraterone acetate, apalutamide, and enzalutamide showed comparable PFS to mCRPC outcomes, while significant differences in early PSA kinetics were observed, with early PSA response serving as a crucial prognostic factor in mHSPC patients.