Real-world comparison of enzalutamide and apalutamide in metastatic hormone-sensitive prostate cancer: a multi-institutional propensity score-matched analysis

Background: Androgen receptor signaling inhibitors (ARSIs) such as enzalutamide (Enz) and apalutamide (Apa), in combination with androgen deprivation therapy (ADT), are standard for metastatic hormone-sensitive prostate cancer (mHSPC). However, direct real-world comparisons, particularly in Japanese populations, are limited. Methods: We retrospectively reviewed 227 mHSPC patients treated with Enz (n = 112) or Apa (n = 115) plus ADT. Propensity score matching (PSM) adjusted for baseline differences. Primary endpoints were prostate-specific antigen (PSA) response, time to castration resistance (TTCR), and overall survival (OS). Results: In the matched cohort after PSM, PSA nadir <0.2 ng/ml was achieved in 63.1% of Enz-treated and 60.3% of Apa-treated patients; ≥90% PSA decline occurred 94.5% and 92.0%, respectively. TTCR and OS were similar between groups (TTCR: P = .415; OS: P = .202). Time to treatment failure (TTF) was significantly shorter with Apa than with Enz (P = .0016). Reduced-dose initiation was more frequent with Apa (22.1% vs 9.8%, P = .0118), and TTCR did not differ across subgroups stratified by treatment and starting dose (P = .8465). Adverse events (AEs) leading to treatment discontinuation were more frequent in the Apa group than in the Enz group (20.9% vs 4.5%). Second-line therapy use after treatment failure was similar (86.4% Enz vs 90.2% Apa), with abiraterone being the most common. Conclusions: In this real-world Japanese cohort, Enz and Apa plus ADT showed comparable PSA responses, TTCR, and OS after PSM; however, Apa was associated with shorter TTF and more frequent AE-related treatment discontinuation. Reduced-dose initiation was more common with Apa without apparent TTCR disadvantage. Given the limited number of events, these findings should be interpreted with caution.