Abiraterone and Enzalutamide Raise Metabolic, Cardiovascular Adverse Event Risks

Older men with advanced prostate cancer receiving abiraterone or enzalutamide have increased risks for metabolic and cardiovascular adverse events, a new study finds.

“With continued expansion of the indications for abiraterone and enzalutamide to earlier stages of the disease continuum, increasing numbers of men will be receiving these therapies for longer periods of time,” Lillian Y. Lai, MD, MS, of the University of Michigan in Ann Arbor and colleagues reported in the Journal of the National Cancer Institute. “This will potentially amplify the scope of men affected and increase the magnitude of the risks of adverse events, making careful attention to management of these issues crucial.”

Among 56,230 patients with advanced prostate cancer receiving Medicare (mean age 76-78 years), 2736 were treated with abiraterone, an androgen synthesis inhibitor, and 2466 with enzalutamide, a nonsteroidal androgen receptor antagonist, along with androgen deprivation therapy. The primary composite outcome was a major metabolic or cardiovascular adverse event, defined as an emergency room visit or hospitalization associated with diabetes, hypertension, or cardiovascular disease while on treatment with abiraterone or enzalutamide. The secondary endpoint was a minor metabolic or cardiovascular adverse event resulting in an outpatient visit while on treatment with these drugs.

Abiraterone treatment was significantly associated with a 77% increased risk of a major composite adverse event and a 24% increased risk of a minor composite adverse event, compared with androgen deprivation therapy alone, Dr Lai’s team reported. By component, abiraterone was significantly associated with an 84% and 37% increased risk for a major or minor diabetic event, respectively, and a 91% and 75% increased risk for a major or minor cardiovascular event, respectively. The investigators noted that abiraterone is taken with a glucocorticoid, which in itself has metabolic and cardiovascular consequences.

Enzalutamide treatment was significantly associated with a 22% increased risk of a major composite adverse event but not a minor composite adverse event, according to the investigators. Abiraterone and enzalutamide did not increase the risk of hypertensive adverse events.

 “As hypothesized, men receiving abiraterone with androgen deprivation were at a significantly increased risk of metabolic and cardiovascular adverse events necessitating emergency room visits and hospitalizations compared with those only on androgen deprivation,” the authors wrote. “Though also statistically significant, the evidence supporting the risks of enzalutamide was weaker, with a smaller magnitude of effect size compared with that associated with abiraterone use.”

Reference

Lai LY, Oerline MK, Caram MEV, Tsao PA, Kaufman SR, Hollenbeck BK, Shahinian VB. Risk of metabolic and cardiovascular adverse events with abiraterone or enzalutamide among men with advanced prostate cancer. J Natl Cancer Inst. Published online April 13, 2022. doi:10.1093/jnci/djac081

This article originally appeared on Renal and Urology News