TOPLINE

Enzalutamide and abiraterone demonstrate comparable overall survival, time to treatment switch, and prostate cancer survival in patients with metastatic castration-sensitive prostate cancer (mCSPC). Among patients aged at least 75 years, enzalutamide was associated with improved overall survival compared with abiraterone, with a 3-year restricted mean survival time (RMST) difference of 1.65 months.

METHODOLOGY

• No clinical trials have directly compared enzalutamide vs abiraterone in the mCSPC setting, and it has remained unclear whether one agent is superior to the other. Researchers conducted a retrospective cohort study using data from the nationwide US Department of Veterans Affairs healthcare system, including patients with mCSPC who initiated enzalutamide (1803 patients) or abiraterone (3332 patients) between January 1, 2020, and December 31, 2023.
• Inverse probability of treatment weighting was used to balance baseline characteristics between treatment groups, including age, race/ethnicity, comorbidities, frailty, treatment initiation year, and prior treatment. 
• Primary outcomes evaluated were overall survival, time to treatment switch or death (TTS), and prostate cancer survival, with RMST differences used to compare patients initiating enzalutamide vs abiraterone. 
• Median follow-up was 18.74 months for abiraterone and 24.76 months for enzalutamide for overall survival; 10.19 months for abiraterone and 11.61 months for enzalutamide for prostate cancer survival; and 10.85 months for abiraterone and 10.95 months for enzalutamide for TTS. 
• Subgroup analyses were conducted in populations defined by prostate-specific antigen (PSA) doubling time (≥ 3 months vs < 3 months), age (≥ 75 years vs < 75 years), and race (non-Hispanic White vs non-Hispanic Black individuals). 

TAKEAWAY

• For overall survival, the 3-year RMST was 27.99 months for enzalutamide and 27.27 months for abiraterone, a difference of 0.72 months. 
• For TTS, the 3-year RMST was 27.34 months for enzalutamide and 26.81 months for abiraterone, a difference of 0.53 months. 
• Among patients aged ≥ 75 years, the 3-year RMST for overall survival was 26.47 months for enzalutamide and 24.82 months for abiraterone, a difference of 1.65 months. 
• In subgroups defined by PSA doubling time or race, no significant differences in RMST were observed between enzalutamide and abiraterone for any of the outcomes. 

IN PRACTICE

“In this nationwide cohort study, enzalutamide and abiraterone yielded comparable [overall survival], TTS, and [prostate cancer survival] outcomes overall, although a small but statistically significant [overall survival] benefit was observed for enzalutamide among older patients (≥ 75 years). These real-world findings from the largest integrated US healthcare system may provide guidance for selecting mCSPC treatments, although residual confounding cannot be fully excluded,” the authors of the study wrote.

SOURCE

The study was led by Jennifer La, PhD, VA Cooperative Studies Program, VA Boston Healthcare System in Boston, and Channing J. Paller, MD, Department of Oncology, Johns Hopkins University School of Medicine in Baltimore. It was published online on July 16 in JCO Clinical Cancer Informatics.

LIMITATIONS

The study cannot directly adjust for unmeasured confounders such as tumor volume, Gleason score, and metastatic burden, which may influence findings. Researchers were unable to confirm concomitant prednisone use among patients receiving abiraterone, although this is a standard clinical practice. Fewer patients were at risk for prostate cancer survival compared with overall survival in later follow-up periods because the data source for cause of death lags behind overall mortality data, resulting in earlier censoring for the prostate cancer survival outcome. The burden of comorbidity is overall high among Veterans, so although comorbidities were balanced across groups in the cohort, results could differ in less comorbid populations.

DISCLOSURES

The study received support from the VA Cooperative Studies Program, DOD CDMRP W81XWH-22-2-0024, DOD CDMRP HT9425-23-1-0464, the American Heart Association, and NIH P30CA006973. La disclosed receiving institutional research funding from Merck and Bayer. Nathanael R. Fillmore, PhD, disclosed receiving institutional research funding from Merck and Bayer. Paller disclosed receiving consulting or advisory fees from Dendreon, Omnitura, Exelixis, AstraZeneca, Janssen Oncology, Pfizer, and Bayer, as well as institutional research funding from Lilly. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.