Real-world comparison of prostate-specific antigen (PSA) response among patients with metastatic castration-sensitive prostate cancer (mCSPC) treated with apalutamide (APA) or enzalutamide (ENZ).

570 Background: Early and sustained PSA reduction ≥90% (PSA90 response) has been associated with improved prognosis among patients treated with APA and ENZ, two androgen receptor pathway inhibitors (ARPIs) approved for mCSPC in combination with androgen deprivation therapy (ADT). Given limited real-world data on early APRI response, this study compared PSA90 at 6 months between APA and ENZ in a nationally representative sample of patients with mCSPC. Methods: A longitudinal cohort analysis of ARPI-naïve patients with mCSPC initiating APA or ENZ identified in linked US healthcare databases (PPS Analytics and Komodo Research Database; 1/1/2016-12/31/2023) was performed. The first APA or ENZ dispensation or pharmacy claim on or after 12/16/2019 defined the index date. Patients were included if they had ≥12 months of pre-index database activity, no other primary cancers, and ≥1 PSA test ≤13 weeks prior to or on the index date. Baseline characteristics were assessed in the 12-month pre-index period. Follow-up spanned from the index date until the earliest of APA or ENZ discontinuation, initiation of a new APRI or radiopharmaceuticals, end of database activity, or end of data. Baseline characteristics (i.e., age, race, region, payer type, index year, time from prostate cancer [PC] diagnosis, time from metastasis, de novo PC, ADT use, first-generation antiandrogen use, chemotherapy use, metastasis locations, Quan-CCI, baseline PSA level, and Gleason score) were balanced between cohorts with inverse-probability of treatment weighting. PSA90 response at 6 months was compared between treatment cohorts using weighted Kaplan-Meier analysis and a Cox proportional hazards model. Results: In total, 1,296 APA and 1,111 ENZ patients were included. Weighted baseline patient characteristics were well-balanced between the treatment cohorts (Table). During follow-up, 81.0% of APA patients and 77.0% of ENZ patients had ≥1 PSA test. At 6 months, APA patients were 20% more likely to achieve PSA90 compared to ENZ patients (hazard ratio [HR] 1.20, 95% CI: 1.07, 1.36; p=0.003; Table). The median time-to-PSA90 response was 3.7 months for APA and 4.9 months for ENZ. Conclusions: Earlier deep PSA response was observed in a significantly higher proportion of ARPI-naïve patients initiating APA relative to ENZ, suggesting larger therapeutic benefit for APA among patients with mCSPC. Weighted patient characteristics. Baseline APAN=1,296 ENZN=1,111 Standardized difference (%) Mean age, years 73.4 73.4 0.3 White (%) 61.8 61.3 1.0 Black (%) 21.6 21.7 0.3 Mean Quan-CCI 8.6 8.6 0.0 Visceral metastasis (%) 17.4 17.7 0.7 De novo PC (%) 53.6 53.7 0.2 Mean PSA level, ng/mL 27.4 27.0 0.7 Follow-up HR (95% CI), P-value PSA90 response at 6 months (%) 61.7 55.2 1.20 (1.07, 1.36) 0.003