Real-world comparative outcomes of abiraterone vs enzalutamide in metastatic castration-sensitive prostate cancer (mCSPC): A propensity-matched analysis from the TriNetX Global Health Research Network.

Abstract

124 Background: Abiraterone acetate (ABI) and enzalutamide (ENZ) have each demonstrated survival benefit in patients with metastatic castration-sensitive prostate cancer (mCSPC), supported by pivotal trials such as LATITUDE, STAMPEDE, and ENZAMET. However, these trials did not directly compare the two agents. Real-world data (RWD) evaluating comparative survival, safety, and rare outcomes such as treatment-emergent neuroendocrine prostate cancer (t-NEPC) remain limited. This study aims to compare clinical outcomes between ABI and ENZ using a global, multicenter RWD. Methods: We conducted a retrospective cohort study using the TriNetX Global Health Research Network, a federated database encompassing electronic medical records from 154 healthcare organizations. Men with mCSPC treated with ABI or ENZ from database inception through June 2025 were identified. Propensity score matching (1:1) was performed based on age, race, ECOG status, PSA, BMI, and comorbidities. The primary outcome was all-cause mortality; secondary outcomes included hospitalization, adverse events (AEs), and incidence of t-NEPC. Time-to-event outcomes were analyzed using Kaplan-Meier and Cox regression methods. Results: Among 5,344 eligible patients (ABI: 2,831; ENZ: 2,513), 2,403 patients were retained in each matched group. The median age was 71.5 years; median follow-up was 426 days (ABI) vs 435 days (ENZ). All-cause mortality was similar between ABI and ENZ (38.49% vs 39.01%; HR 1.006, 95% CI: 0.918–1.102; p = 0.862). Hospitalization rates (46.65% vs 44.99%; p = 0.247) and Kaplan-Meier survival curves were not significantly different (log-rank p = 0.9002). Fatigue (31% ABI vs 34% ENZ) and falls (7% vs 8%) were slightly more common with ENZ, while hypertension was marginally higher in the ABI group (2% vs 1.8%). The incidence of t-NEPC was nearly identical (ABI: 18.67% vs ENZ: 18.76%; RR 0.996, 95% CI: 0.886–1.119; p = 0.94). Docetaxel exposure was similar across both cohorts (ABI: 15% vs ENZ: 16%), suggesting comparable use of subsequent lines of therapy. Conclusions: In this large, global real-world cohort of mCSPC patients, abiraterone and enzalutamide showed comparable survival and hospitalization outcomes, with no significant differences in t-NEPC transformation. This data supports therapeutic equivalence and suggests treatment selection may be best guided by individual patient factors, tolerability profiles, and shared decision-making.