Overall survival (OS) in elderly, frail, or high comorbidity veterans receiving androgen receptor pathway inhibitors (ARPIs) with androgen-deprivation therapy (ADT) vs ADT alone for de novo metastatic castration-sensitive prostate cancer (mCSPC).

103 Background: Clinical trials and real-world analyses have shown that combining an ARPI (abiraterone, apalutamide, darolutamide, or enzalutamide) + ADT improves survival vs ADT alone in patients with mCSPC. However, limited data exist on the impact of ARPI + ADT in patients who are elderly, frail, or who have a high comorbidity burden, since these patients are underrepresented in clinical trials. This real-world study evaluated characteristics and OS in this unique cohort of patients with de novo mCSPC. Methods: This observational cohort study used Veterans Health Administration electronic medical records to compare OS and patient characteristics in veterans with de novo mCSPC treated with ARPI + ADT vs ADT alone. Patients were ≥75 years of age, had a Veterans Affairs Frailty Index (VA-FI) score >0.2, or had a Charlson Comorbidity Index (CCI) score ≥3. Patients were indexed on their first claim for ADT between June 01, 2017, and December 31, 2022, and followed until censoring on June 01, 2025, or death. A multivariable, time-varying Cox model, adjusted for age, body mass index, CCI, and prostate-specific antigen (PSA) level, was used to estimate mortality risk and account for time between ADT and ARPI initiation. Results: Of 2398 total patients, 1037 (43.2%) received ARPI + ADT and 1361 (56.8%) received ADT alone. Median follow-up was 27.1 months. Compared to ADT alone, patients receiving ARPI + ADT were younger (median age 76.7 vs 81.2 years; SMD: -0.43), had a lower comorbidity burden (CCI ≥3: 49.0% vs 55.2%; SMD: 0.19), were less frail (VA-FI >0.2: 66.5% vs 71.5%; SMD: 0.11), and had a similar median PSA level (121.3 ng/mL vs 130.0 ng/mL; SMD: 0.02). ARPI + ADT was associated with a significantly lower risk of death (adjusted hazard ratio [aHR]: 0.81; 95% confidence interval [CI]: 0.74–0.90; P