Identical Survival for Abiraterone and Enzalutamide in Vets With Metastatic Hormone-Sensitive Prostate Cancer

Abiraterone and enzalutamide showed identical survival outcomes when used as first-line treatment for metastatic hormone-sensitive prostate cancer (mHSPC), according to a new study using US Department of Veterans Affairs (VA) data. The report represents the first head-to-head clinical analysis of these commonly used androgen receptor inhibitors.

Among 1258 veterans treated with abiraterone and 311 treated with enzalutamide, median overall survival was 36.2 months for both drugs. Patients were followed for a mean of 28.7 months (abiraterone) and 30.8 months (enzalutamide), reported by Martin W. Schoen, MD, MPH, from Saint Louis University School of Medicine and the St. Louis VA Medical Center, in JAMA Network Open. 

Notably, there was no significant difference in outcomes among Black veterans, who often have poorer outcomes in prostate cancer, and in patients with cardiovascular disease.

“This is the first direct comparison of abiraterone and enzalutamide for mHSPC in a clinical practice setting,” Schoen told Federal Practitioner. “At the population level, there are no differences based on initial treatment choice.”

Abiraterone Is Preferred in the VA Due to Cost

According to Schoen, abiraterone and enzalutamide are the most commonly used androgen receptor inhibitors to treat mHSPC within the VA. A 2025 study by Schoen and colleagues found that 53.7% of veterans with mHSPC in 2022 received androgen receptor inhibitor therapy, up from 16.9% in 2017. 

“In the VA, the preference for most patients is abiraterone since it is the least expensive agent,” he said. A generic version has been available for several years.

Additionally, abiraterone “has been on the market for the longest, and therefore clinicians are familiar with its use,” Schoen said. However, “clinicians have little idea of the comparative efficacy between these 2 agents,” he added.

The authors suggest that the cost and toxicities of the medications should guide clinician decisions, Schoen said. “There is data that abiraterone may worsen diabetes, since it is given with prednisone and could increase the risk of cardiovascular events,” he said.

He added that 2 newer drugs, apalutamide and darolutamide, are also “viable options.” Chemotherapies and certain targeted drugs are also available, “but they are only used in a select group of patients.”

Outside Specialist: Diverse Study Population Is a Plus

Hematologist-oncologist Natalie Reizine, MD, of the University of Illinois College of Medicine, Chicago, who was not involved in the study, told Federal Practitioner that the real-world data are valuable given the limitations of clinical trial populations.

“It’s difficult to compare clinical trials because they enroll different groups of patients,” she said. And, she said, they often exclude patients with significant comorbidities. “If they have bad cardiovascular disease, for instance, or poorly controlled diabetes, they're excluded from the clinical trial. But in real life, many of our patients have other medical problems that we have to manage.”

Reizine also emphasized the significance of the study’s diverse patient population. “Black men are very underrepresented in clinical trials. Many clinical trials that lead to drug approval will have only few or no Black men at all, yet these drugs go on to be widely prescribed to all men with prostate cancer.”

Results Are ‘Reassuring’

Reizine described the overall study findings as “reassuring,” especially in light of “studies that show that abiraterone and prednisone may be associated with worse cardiovascular outcomes. This study showed that in this VA population, even for patients who had cardiovascular disease, there was not a difference in how they did.”

As for choosing between agents, she recommended considering comorbidities and potential drug-drug interactions. “One of the big reasons that you may not be able to safely prescribe enzalutamide, for instance, is if a patient is on an anticoagulant, which is incredibly common in cancer patients. Enzalutamide has more drug-drug interactions than abiraterone and prednisone.” 

Study Demographics and Findings

The study included all patients with mHSPC who initiated abiraterone or enzalutamide between July 2017 and April 2023.

Median ages were 73 (abiraterone) and 74 years (enzalutamide, P = .29). Racial distribution was similar between groups: abiraterone (68.1% White, 25.0% Black, 6.9% other/unknown) and enzalutamide (66.6% White, 27.0% Black, 6.4% other/unknown; P = .74). Ethnicity was 89.2% non-Hispanic, 4.4% Hispanic, and 6.4% unknown in the abiraterone group vs 88.4% non-Hispanic, 3.5% Hispanic, and 8.0% unknown in the enzalutamide group (P = .50).

The groups had similar rates of the most common comorbidities: diabetes (40.5% vs 46.3%, respectively, P = .07), peripheral vascular disease (40.2% vs 37.6%, respectively, P = .44), and chronic pulmonary disease (37.0% vs 40.5%, P = .29).

In an inverse probability weighting analysis with abiraterone as reference, weighted median overall survival was comparable across the entire cohort (36.2 months, P = .32), Black veterans (39.7 months, P = .90), and those with cardiovascular disease (31.5 months, P = .30).

The authors noted limitations such as the observational cohort design and data constraints. 

The study was supported by the American Society of Clinical Oncology Conquer Cancer Foundation, the Prostate Cancer Foundation, and the Blavatnik Family Foundation.

Schoen discloses relationships with the Prostate Cancer Foundation, Astellas, and US Department of Defense. Other authors disclose relationships with the American Society of Clinical Oncology, Pfizer, Exelixis, Eli Lilly, Sanofi, Merck, Seagen, Bellicum, and BMS.

Outside the submitted work. Reizine discloses relationships with the US Department of Defense, Sanofi, Exelexis, Janssen, AstraZeneca, EMD Serono, Janssen, Merck, and Tempus.