Risk of Metabolic and Cardiovascular Adverse Events With Abiraterone or Enzalutamide Among Men With Advanced Prostate Cancer

Abstract

Background: Abiraterone and enzalutamide are the most common oral agents for the treatment of men with advanced prostate cancer. To understand their safety profiles in real-world settings, we examined the association between the use of abiraterone or enzalutamide and the risk of metabolic or cardiovascular adverse events while on treatment.

Methods: Men with advanced prostate cancer and their use of abiraterone or enzalutamide were identified in a 20% sample of the 2010-2017 national Medicare claims. The primary composite outcome was the occurrence of a major metabolic or cardiovascular adverse event, defined as an emergency room visit or hospitalization associated with a primary diagnosis of diabetes, hypertension, or cardiovascular disease. The secondary composite outcome was the occurrence of a minor metabolic or cardiovascular adverse event, defined as an outpatient visit associated with a primary diagnosis of the aforementioned conditions. Risks were assessed separately for abiraterone and enzalutamide using Cox regression. All statistical tests were 2-sided.

Results: Compared with men not receiving abiraterone, men receiving abiraterone were at increased risk of both a major composite adverse event (hazard ratio [HR] = 1.77, 95% confidence interval [CI] = 1.53 to 2.05; P < .001) and a minor composite adverse event (HR = 1.24, 95% CI = 1.05 to 1.47; P = .01). Compared with 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 to 1.48; P = .04) but not a minor composite adverse event (HR = 1.04, 95% CI = 0.83 to 1.30; P = .75).

Conclusion: Careful monitoring and management of men on abiraterone or enzalutamide through team-based approaches are critical.

Figure 1.

Event-free survival rates for (A) primary composite outcome and (B) secondary composite outcome among men with advanced prostate cancer according to abiraterone use. Men receiving abiraterone had lower event-free rates for both primary and secondary composite outcomes compared with men not receiving abiraterone (log-rank test P < .001 and P = .01, respectively). All statistical tests were 2-sided.

Figure 2.

Event-free survival rates for (A) primary composite outcome and (B) secondary composite outcome among men with advanced prostate cancer according to enzalutamide use. Men receiving enzalutamide and men not receiving enzalutamide had similar event-free rates for both primary and secondary composite outcomes (log-rank test P = .11 and P = .84, respectively). All statistical tests were 2-sided.