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).

Abstract

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 <0.001) vs ADT alone. Median OS was 33.0 months (95% CI: 30.2–35.9) for ARPI + ADT and 23.3 months (95% CI: 21.4–25.1) for ADT alone. Significant improvements in OS were consistent among age, CCI, and VA-FI subgroups (Table). Conclusions: In this real-world cohort of veterans with de novo mCSPC who were elderly, frail, or who had a high comorbidity burden, ARPI + ADT was associated with significantly longer OS in overall and subgroup analyses. These findings support the use of ARPI + ADT in this patient population. Subgroup ARPI + ADTMedian survival, months (95% CI), n ADT aloneMedian survival, months (95% CI), n aHR (95% CI) a , P value Age ≥75 years 33.1 (29.6–36.7),n = 645 22.7 (20.6–24.7),n = 995 0.85 (0.75–0.96), P <0.01 CCI score ≥3 29.0 (24.9–33.1),n = 508 19.6 (17.8–21.4),n = 751 0.75 (0.65–0.86), P <0.001 VA-FI score >0.2 27.1 (24.2–30.0),n = 690 19.7 (18.0–21.4),n = 973 0.81 (0.72–0.91), P <0.001 a ADT = reference group.