JCO Clin Cancer Inform. 2026 Jul-Sep;10(3):e2500213. doi: 10.1200/CCI-25-00213. Epub 2026 Jul 16.
ABSTRACT
PURPOSE: Enzalutamide or abiraterone, combined with androgen-deprivation therapy, is standard of care for metastatic castration-sensitive prostate cancer (mCSPC). However, no trials have compared these drugs. This study compared clinical outcomes in patients with mCSPC treated with enzalutamide or abiraterone.
METHODS: This retrospective cohort study included patients with mCSPC initiating enzalutamide or abiraterone between January 1, 2020, and December 31, 2023, within the nationwide US Veterans Affairs health care system. Inverse probability of treatment weighting was used to balance baseline characteristics. Restricted mean survival time (RMST) differences in overall survival (OS), time to treatment switch or death (TTS), and prostate cancer survival (PCS) were evaluated.
RESULTS: The study included 5,135 patients with mCSPC treated with enzalutamide (1,803) or abiraterone (3,332). The median age was 74.33 years; 58.0% were non-Hispanic White, 28.2% non-Hispanic Black, and 5.6% Hispanic. After weighting, baseline characteristics were well balanced. The median follow-up was 18.74 months for abiraterone and 24.76 months for enzalutamide. Outcomes were similar overall: for OS, the 3-year RMST difference was 0.72 months (95% CI, -0.06 to 1.50); for TTS, the 3-year RMST difference was 0.53 months (95% CI, -0.45 to 1.51), and for PCS, the 1-year RMST difference was -0.12 months (95% CI, -0.35 to 0.11). In subgroup analysis, enzalutamide was associated with improved OS among patients age 75 years and older (3-year RMST difference: 1.65 months, 95% CI, 0.41 to 2.89), but not among younger patients (3-year RMST difference: 0.13 months, 95% CI, -0.86 to 1.11).
CONCLUSION: In this nationwide cohort study, enzalutamide and abiraterone yielded comparable OS, TTS, and PCS outcomes overall, although a small but statistically significant OS benefit was observed for enzalutamide among older patients (≥75 years). These real-world findings from the largest integrated US health care system may provide guidance for selecting mCSPC treatments, although residual confounding cannot be fully excluded.
PMID:42462188 | DOI:10.1200/CCI-25-00213
