Androgen-receptor pathway inhibitors triplet therapy (ARAAT): Real-world outcomes in metastatic hormone-sensitive prostate cancer.

82 Background: Darolutamide or abiraterone, in combination with androgen-deprivation therapy (ADT) and docetaxel (DOC) is recommended as a treatment strategy in patients with metastatic hormone-sensitive prostate cancer (mHSPC). In this study (ARAAT), we report clinical outcomes in patients with mHSPC treated with triplet therapy consisting of darolutamide + ADT + DOC (DAR) or abiraterone + ADT + DOC (ABI). Methods: This retrospective cohort analysis used the ConcertAI Patient360 database, a geographically diverse US oncology electronic medical record dataset. Adult patients with mHSPC who initiated triplet therapy with DAR or ABI from January 2020 and January 2025 were included. Inverse probability of treatment weighting (IPTW) and multivariate Cox proportional hazard models were applied to account for baseline confounding factors. Endpoints were overall time to treatment discontinuation (TTD) due to any cause, time to castration-resistant progression-free survival (mCRPC or death), time to PSA <0.2 ng/mL (including Kaplan-Meier estimated rates of PSA <0.2 ng/mL), time to next treatment (TTNT), and overall survival. Results: A total of 592 pts with mHSPC initiated DAR (n=368) or ABI (n=224). Median baseline PSA was 53 ng/mL in the DAR cohort and 35 ng/mL in the ABI cohort. Median follow-up was 19 months in both the cohorts. In IPTW analysis, TTD (Hazard ratio HR 0.63), time to mCRPC or death (HR 0.73), TTNT (HR 0.54), and OS (HR 0.68) were significantly longer with DAR vs ABI (Table). The probability of PSA <0.2 ng/mL after 12 months was 61.6% (95% CI 55.2, 68.1) with DAR vs 52.6% (95% CI 43.7, 62.1) with ABI and 72.0% (95% CI 64.4, 79.2) with DAR vs 59.9% (95% CI 49.8, 70.2) with ABI after 24 months. Time to PSA <0.2 ng/mL was significantly shorter with DAR (HR 1.34; Table). The trend in results were consistent using multivariate Cox proportional hazard models (Table). Conclusions: In this real-world study, patients receiving darolutamide triplet therapy had significantly improved outcomes over abiraterone triplets, including TTD, time to mCRPC or death, TTNT, PSA response, and OS after adjustment for confounding factors. Endpoint (DAR vs ABI) IPTW modelHR (95% CI); P-value Multivariate Cox Proportional Hazard † HR (95% CI); P-value TTD 0.63 (0.53, 0.76); <0.001 0.65 (0.49, 0.85); 0.002 Time to mCRPC or death 0.73 (0.63, 0.86); <0.001 0.77 (0.60, 0.98); 0.033 TTNT 0.54 (0.44, 0.67); <0.001 0.57 (0.41, 0.79); <0.001 Time to PSA <0.2 ng/mL* 1.34 (1.10, 1.62); 0.003 1.46 (1.07, 1.99); 0.018 OS 0.68 (0.54, 0.86); 0.001 0.67 (0.48, 0.96); 0.026 *Model carried out in pts (DAR n=255; ABI n=143) with baseline PSA ≥1 and ≥1 PSA measurement during follow-up. † Directly adjusted model.