A retrospective cohort study of US veterans with metastatic hormone-sensitive prostate cancer (mHSPC) found no significant differences in prostate-specific antigen (PSA)–derived tumour growth rates (g-rates) or overall survival (OS) between patients treated with abiraterone acetate and those treated with enzalutamide as first-line androgen-targeted therapy.
The analysis, led by Dr Harshraj Leuva and colleagues, used data from the Veterans Affairs Health Care System and included 1,569 veterans who initiated abiraterone or enzalutamide between July 2017 and April 2023; data were analysed from April 2024 through March 2025.
Cohort characteristics
Of the total cohort, 1,258 patients received abiraterone (median age 73 years; IQR 69–79) and 311 patients received enzalutamide (median age 74 years; IQR 69–79). Racial composition was: abiraterone 314 African American (25.0%), 857 White (68.1%), 87 other/unknown (6.9%); enzalutamide 84 African American (27.0%), 207 White (66.6%), 20 other/unknown (6.4%).
Tumour growth and survival outcomes
In the unweighted analysis, median PSA-based g-rates were identical to three significant figures: 0.000137/day for both cohorts (abiraterone IQR 0.000094–0.001519; enzalutamide IQR 0.000098–0.001815). Unweighted median OS was 36.2 months in both groups (abiraterone 36.2 months; 95% CI, 32.8–38.8; enzalutamide 36.2 months; 95% CI, 34.1–40.5). Median follow-up was 28.7 months (IQR 15.6–45.6) in the abiraterone group and 30.8 months (IQR 16.1–39.1) in the enzalutamide group.
Using inverse probability weighting (IPW) to adjust for baseline differences and potential confounders, the weighted median OS (abiraterone as reference) remained comparable: 36.2 months (95% CI, 32.8–38.8) for abiraterone versus 35.5 months (95% CI, 32.9–40.4) for enzalutamide (hazard ratio [HR], 1.09; 95% CI, 0.92–1.30; P = .32). Measured g-rates were similarly comparable between agents.
Subgroup analyses
Results were consistent across clinically relevant subgroups. Among African American veterans the weighted median OS was 39.7 months (95% CI, 34.3–46.6) for abiraterone versus 40.3 months (95% CI, 34.3–not reached) for enzalutamide (HR, 0.98; 95% CI, 0.72–1.34; P = .90). In patients with cardiovascular disease, weighted median OS was 31.5 months (95% CI, 28.1–35.5) for abiraterone versus 35.0 months (95% CI, 30.7–38.9) for enzalutamide (HR, 1.12; 95% CI, 0.91–1.37; P = .30).
In a 1:1 exact-matched analysis (n = 279 in each group), 63 patients (23%) in each arm were African American. Median follow-up in the matched cohorts was 27.3 months (IQR, 15.3–40.8) for abiraterone and 31.1 months (IQR, 16.8–39.9) for enzalutamide. The matched cohorts were balanced for high-risk tumour features: 158 patients (57%) in each arm had an initial Gleason score ≥8, and 224 patients (80%) in each arm had a baseline PSA ≥50 ng/mL. In the matched cohort and in subgroup analyses by race, Gleason score, and baseline PSA, there were no statistically significant differences in median g-rate or OS between abiraterone and enzalutamide.
Interpretation and clinical relevance
The authors conclude that in this real-world veterans cohort, abiraterone and enzalutamide produced similar PSA-derived tumour growth rates and overall survival when used as first-line therapy for mHSPC, including among African American patients and those with significant comorbid cardiovascular disease or high-risk disease features.
These data support that the choice of agent may be reasonably guided by comorbidity profile, adverse-effect risk, drug interactions, access and cost considerations, and patient preference, rather than by expected differences in oncologic efficacy.
Limitations
As a retrospective, observational study, residual confounding remains possible despite IPW and exact matching. Follow-up duration is moderate; some subgroup medians were not reached. The analysis focused on PSA-derived growth rates and OS; detailed adverse-event profiles, quality-of-life measures, subsequent therapies, and sequencing were not presented in the abstract and may affect real-world decision-making.
Paper: Leuva H, Zhou M, Teply BA, et al. Abiraterone vs Enzalutamide Among US Veterans With Metastatic Hormone-Sensitive Prostate Cancer. JAMA Netw Open. 2025;8(11):e2540730. doi:10.1001/jamanetworkopen.2025.40730 Access online here.
