AUA 2022: Risk of Metabolic and Cardiovascular Adverse Events with Abiraterone or Enzalutamide Among Men with Advanced Prostate Cancer

( In a moderated poster presentation at the 2022 American Urologic Association Annual Meeting held in New Orleans and virtually, Dr. Lillian Lai discussed the risk of metabolic and cardiovascular toxicity in men receiving abiraterone or enzalutamide for advanced prostate cancer. Each of these treatments, along with ongoing androgen deprivation therapy (ADT), are guidelines indicated for the management of men with advanced prostate cancer. Each of these agents acts through inhibition of the androgen receptor pathways, conferring anti-androgenic properties. Further, abiraterone is co-prescribed with prednisone, which may contribute to metabolic or cardiovascular adverse events. Using real-world data, the authors sought to understand the safety of abiraterone and enzalutamide use by examining the risk of metabolic or cardiovascular events while on treatment.

To do so, the authors identified 56,230 men with advanced prostate cancer in a 20% sample of the 2011-2017 national Medicare claims. They considered abiraterone or enzalutamide use as a time-dependent covariate with the primary analytic outcome of the occurrence of a major metabolic or cardiovascular event. This was defined as an emergency room visit or hospitalization associated with a primary diagnosis of diabetes, hypertension, or cardiovascular disease. The secondary outcome was the occurrence of a minor metabolic or cardiovascular event, defined as an outpatient visit associated with a primary diagnosis of the aforementioned conditions. The occurrence of adverse events by specific diagnoses was also examined individually. The authors examined men who experienced an event of interest in the 12 months prior to the study start date. Cox proportional hazards regression models were used to examine treatment related differences in the risks of primary and secondary composite outcomes.

The authors found that using unadjusted incidence rates, men receiving abiraterone had 1 additional emergency room visit/hospitalization due to a cardiovascular event for every 29 men treated (median time on drug: 4.7 months). 

Thus, based on Cox proportional hazards models, compared to men not receiving abiraterone, men receiving the drug were at increased risk of both a major composite adverse event (HR 1.77 95% CI 1.53-2.05 p <0.01) and a minor composite adverse event (HR 1.24 95% CI 1.05-1.47 p=0.01). 

Similarly, compared to men not receiving enzalutamide, men receiving enzalutamide were at an increased risk of a major composite adverse event (HR 1.22 95% CI 1.01-1.48 p=0.04). Interestingly, these men were not at significantly increased risk of a minor composite adverse event (HR 1.04 95% CI 0.83-1.30 p=0.75).

The authors, therefore, conclude that treatment with abiraterone or enzalutamide is associated with increased risk of major metabolic or cardiovascular events in real-world settings.

Presented by: Lillian Lai, MD, MS, University of Michigan

Written by: Christopher J.D. Wallis, University of Toronto Twitter: @WallisCJD during the 2022 American Urological Association (AUA) Annual Meeting, New Orleans, LA, Fri, May 13 – Mon, May 16, 2022

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