Abiraterone vs Enzalutamide Among US Veterans With Metastatic Hormone-Sensitive Prostate Cancer

Importance The choice of first line hormonal therapy in metastatic hormone-sensitive prostate cancer (mHSPC) is often based on comorbidities or physician preference due to the lack of data comparing abiraterone and enzalutamide in clinical trials and in clinical practice settings, especially in African American patients. Objective To compare clinical outcomes in patients with mHSPC treated with abiraterone acetate or enzalutamide. Design, Setting, and Participants This cohort study included all patients with mHSPC diagnoses in the US Veterans Affairs Health Care system who initiated abiraterone or enzalutamide between July 2017 and April 2023. Data were analyzed from April 2024 to March 2025. Exposures Receipt of abiraterone acetate or enzalutamide. Main outcomes and measures Drug outcomes were established by estimating rates of tumor growth ( g -rates) using prostate-specific antigen (PSA) values while receiving therapy and measuring overall survival (OS). Two different matching analyses were performed: inverse probability weighting (IPW) and 1:1 exact matching. Results A total of 1258 patients (median [IQR] age, 73 [69-79] years; 314 [25.0%] African American, 857 [68.1%] White, and 87 [6.9%] with other or unknown race) who received abiraterone and 311 patients (median [IQR] age, 74 [69-79] years; 84 [27.0%] African American, 207 [66.6%] White, and 20 [6.4%] with other or unknown race) who received enzalutamide were included. In the unweighted analysis, the abiraterone cohort had median (IQR) g -rate of 0.000137/d (0.000094-0.001519) and the enzalutamide cohort, 0.000137/d (0.000098-0.001815); median (IQR) OS was 36.2 (32.8-38.8) months for abiraterone and 36.2 (34.1-40.5) months for enzalutamide, with a median (IQR) follow-up of 28.7 (15.6-45.6) and 30.8 (16.1-39.1) months, respectively. In IPW analysis, using abiraterone as reference, the weighted median OS was comparable between abiraterone and enzalutamide in the full cohort (36.2; 95% CI, 32.8-38.8 vs 35.5; 95 % CI, 32.9-40.4 months; hazard ratio [HR], 1.09; 95% CI, 0.92-1.30; P = .32), African American veterans (39.7; 95% CI, 34.3-46.6 vs 40.3; 95% CI, 34.3-not reached months; HR, 0.98; 95% CI, 0.72-1.34; P = .90) and those with cardiovascular disease (31.5; 95% CI, 28.1-35.5 vs 35.0; 95% CI, 30.7-38.9; HR, 1.12; 95% CI, 0.91-1.37; P = .30). In 1:1 matched analysis, both the abiraterone and enzalutamide groups had 279 patients with 63 (23%) who were African American; these patients had a median (IQR) follow-up of 27.3 (15.3-40.8) and 31.1 (16.8-39.9) months, respectively. The 1:1 matched cohort consisted of 158 patients (57%) in each group with an initial Gleason score of 8 or higher, and 224 patients (80%) in each group with a PSA value of 50 ng/mL or higher at treatment initiation. For the 1:1 matched cohort and its subgroups of African American patients, patients with Gleason scores of 8 or higher, and patients with a starting PSA level of 50 ng/mL or higher, no statistically significant difference in median g -rate and OS was observed. Conclusions and Relevance This cohort study found that abiraterone and enzalutamide had comparable outcomes in a first-line mHSPC setting, with similar g -rates and OS in both White and African American patients. There were no differences in survival or g -rate between treatment based on race, comorbidities, and prostate cancer features, including Gleason score, PSA, and volume of disease.