Comparison of docetaxel triplet therapy with androgen receptor pathway inhibitor (ARPI) doublet in US veterans with metastatic hormone sensitive prostate cancer (mHSPC).

185 Background: Combination therapy has improved survival in clinical trials of mHSPC, but there are no head-to-head studies comparing docetaxel triplet and ARPI doublet therapy. The ARASENS and PEACE-1 trials showed survival benefit with darolutamide or abiraterone added to ADT and docetaxel. This study compares overall survival (OS) between docetaxel triplet and ARPI doublet in a real-world veteran cohort based on disease presentation and ARPI used. Methods: A retrospective study of US veterans with mHSPC treated with an ARPI (abiraterone, enzalutamide, apalutamide, darolutamide) within 4 months of diagnosis after July 1, 2021. Docetaxel triplet therapy was defined as docetaxel given within 90 days of ARPI. Veterans were grouped by disease presentation (synchronous vs metachronous) and volume of disease (high vs low), using CHAARTED criteria. Propensity score matching (caliper 0.05) was performed by age, highest PSA within 6 months, and disease volume. OS was compared using Cox proportional hazard models, with subgroup analyses by presentation, volume, and by ARPI type (abiraterone vs. darolutamide). Results: After matching, 608 veterans were identified with no significant baseline differences. With a median follow-up of 24.1 months, median OS not reached in either group. Triplet therapy was associated with decreased risk of death vs doublet therapy (HR 0.60, 95% CI 0.43-0.82). Survival benefit was greatest in synchronous disease (n=508, HR 0.51, 95% CI 0.35-0.74) and high volume disease (n=428, HR 0.55, 95% CI 0.38-0.79), with no difference in metachronous (HR 1.00, 95% CI 0.49-2.03) or low volume cases (HR 0.77, 95% CI 0.38-1.54). Among triplet patients treated with abiraterone or darolutamide, darolutamide (n=190) showed improved OS vs abiraterone (n=101), (HR 0.52, 95% CI 0.30-0.91). Conclusions: In this real-world cohort, docetaxel triplet therapy was associated with lower mortality than ARPI doublet, particularly in de novo and high-volume mHSPC. Exploratory analysis suggested darolutamide triplet was associated with decreased mortality compared to abiraterone. These findings support the role of docetaxel triplet therapy in selected patients with high-volume, de novo mHSPC, though prospective validation is warranted. Baseline characteristics of matched cohort. Mean age High volume Synchronous Median PSA (highest, ng/mL) Docetaxel triplet n=305 69.0 70.5% 81.6% 107 ARPI doublet n=303 69.4 70.3% 85.5% 84.9