Mortality Risk for Patients With Preexisting Cardiovascular Conditions Treated With Abiraterone Acetate or Enzalutamide
A new population-based study showed that novel oral androgen signaling–inhibitor therapies may be associated with an increased risk of death in patients with preexisting cardiovascular conditions. The research was published by Lu-Yao et al in European Urology.
“Data from published clinical trials revealed a small but significant increase in the incidence of cardiovascular toxicity in patients treated with androgen-deprivation therapy,” said corresponding study author Grace Lu-Yao, PhD, MPH. “However, little was known about the short-term mortality in men with cardiovascular risk factors treated with these novel oral androgen signaling–inhibitor therapies, especially among patients who did not qualify for clinical trials.”
“This study fills that major knowledge gap: what are the clinical outcomes of men with advanced prostate cancer and preexisting cardiovascular conditions treated with these novel oral androgen inhibitor therapies? The outcomes of this study provide new relevant data to facilitate patient-physician discussions about the risks and benefits of treatment for men with advanced prostate cancer,” she continued.
Methods
Men with advanced prostate cancer that progressed on androgen-deprivation therapy are typically treated with novel androgen signaling–inhibitor therapies such as abiraterone acetate and enzalutamide. Many of the pivotal studies which led to the approval of these therapies excluded men with multiple cardiovascular comorbidities. As a result, the risk in these patients is poorly understood.
In order to explore this question, researchers conducted a large-scale population-based study. The team examined data from 3,876 patients with advanced prostate cancer collected in the Surveillance, Epidemiology, and End Results (SEER) database. Sixty-seven percent of the men treated with abiraterone acetate or enzalutamide had at least one preexisting cardiovascular condition—such as congestive heart failure, acute myocardial infarction, stroke, atrial fibrillation, and ischemic heart disease—in addition to prostate cancer.
Findings
The results showed a higher 6-month mortality after starting androgen-inhibition therapy in patients who had preexisting cardiovascular conditions.
To explore that result in finer detail, the researchers examined the outcomes by chemotherapy use. They found that compared to patients receiving the same therapy for prostate cancer without preexisting cardiovascular conditions, those with at least three heart conditions had a 43% increase in the relative risk of 6-month mortality (if they had chemotherapy before using the oral androgen signaling–inhibitor therapy) and a 56% increase in the relative risk of 6-month mortality among patients without documented chemotherapy use. In essence, having three or more preexisting cardiovascular conditions was associated with roughly a 50% increase in mortality.
In addition, the researchers examined changes in hospitalization rates following the use of the two oral androgen inhibitors. Among the no-chemotherapy group, abiraterone acetate was associated with an increase in posttreatment hospitalization, but the same pattern was not observed in patients treated with enzalutamide. Among patients with at least three preexisting cardiovascular conditions and no history of chemotherapy, enzalutamide was associated with a 41% lower posttreatment hospitalization rate compared to abiraterone acetate.
The researchers found that abiraterone acetate is associated with increased hospitalizations in patients taking various classes of medications. “In addition to blocking androgen synthesis, abiraterone acetate may interact with many drugs and lead to higher risk of toxicity from a wide range of other medications,” said Dr. Lu-Yao. “Further studies are warranted to understand the potential mechanisms underlying the observations.”
In response to the study’s findings, researchers are working with cardiologists to monitor the risk of adverse cardiovascular events and develop alternative treatment strategies.
Disclosures: This project was supported in part by the Department of Health of Pennsylvania, the National Institutes of Health/National Cancer Institute, and the Sidney Kimmel Cancer Center Biostatistics Shared Resource. For full disclosures of the study authors, visit europeanurology.com.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
