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.