PSA nadir–stratified outcomes of ARPI doublet and docetaxel triplet therapy in metastatic prostate cancer.

e17096 Background: Therapy intensification has expanded combination strategies in metastatic prostate cancer (mPC) with improved outcomes in clinical trials. However, it remains unclear which patients derive incremental benefit from the addition of upfront docetaxel to androgen receptor pathway inhibitor (ARPI)–based doublet therapy. Methods: We identified adults with prostate cancer in the Patient360 Prostate dataset, a U.S.-based de-identified data source derived from electronic health records, linked claims, and mortality data. Patients initiating ARPI doublet (ARPI + androgen deprivation therapy ADT), docetaxel doublet (docetaxel + ADT), or triplet (ARPI + ADT + docetaxel) were included. Patient characteristics and treatment regimens were summarized descriptively; overall survival (OS) was estimated using Kaplan–Meier methods. Results: Patients with mPC were diagnosed between 1990 and 2025. Among patients without privacy-compliant date of birth suppression, median age was 67 years; 79.4% were White and 14.3% Black. ECOG performance status was 0–1 in 86.4%. ARPI doublet was the most common regimen (n = 7,676), followed by triplet (n = 1,389) and docetaxel doublet (n = 1,282; total n = 10,347). Compared with ARPI doublet, patients who received docetaxel-containing regimens had higher prevalence of adverse baseline features, including de novo metastatic disease (triplet 65.7%; docetaxel doublet 68.4% vs ARPI doublet 55.2%), liver metastases (14.8% and 17.9% vs 8.7%), and high-grade disease (Gleason 8–10: 55.5% and 57.2% vs 49.2%). Bone-supportive therapy use was also higher (66.7% and 73.4% vs 56.9%, respectively). A PSA nadir 200 ng/mL (HR 1.39), and Gleason score 8–10 (all p < 0.0001). Conclusions: In the largest cohort to date comparing ARPI doublet and triplet therapy, ARPI doublet was the most common regimen and was associated with more favorable outcomes, even after multivariable adjustment. Non-achievement of PSA nadir identifies a population with poorer survival in whom docetaxel triplet therapy may be associated with improved outcomes, supporting the rationale underlying the TRIPLE-SWITCH (SWOG/CCTG-PR26) clinical trial.