The study find that  A new large population-based study from the Sidney Kimmel Cancer Center Jefferson Health shows that novel oral androgen signaling inhibitor therapies are associated with an increased risk of death in patients with pre-existing cardiovascular conditions. The research is publish in the journal European Urology. “Data from published clinical trials  reveal a small but significant increase in the incidence of cardiovascular toxicity in patients treated with androgen deprivation therapy;” says corresponding author Grace Lu-Yao, Ph.D., MPH, professor and vice chair of medical oncology at Thomas Jefferson University and associate director of population science at the Sidney Kimmel Cancer Center Jefferson Health.

Androgen deprivation therapy

“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 pre-existing cardiovascular conditions treated with these novel oral androgen inhibitor therapies?” says Dr. Lu-Yao.

“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.” Men with advanced prostate cancer that progressed on androgen deprivation  therapy (ADT); are typically treat 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 co-morbidities. As a result; the risk in these patients is poorly understood.

Multiple cardiovascular co-morbidities

In order to explore this question, Dr. Lu-Yao and colleagues 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, which covers about 30% of the US population. Sixty-seven percent of the men treated with abiraterone acetate or enzalutamide had at least one pre-existing cardiovascular condition; (such as congestive heart failure; acute myocardial infarction, stroke, atrial fibrillation and ischemic heart disease) in addition to prostate cancer.

The results showed a higher 6-mortality after starting androgen-inhibition therapy in patients who had pre-existing cardiovascular conditions. To explore that result in finer detail; the study examined the outcomes by chemotherapy use; since patients whose cancers no longer respond to chemotherapy tend to have more advanced disease and shorter life expectancy than those who have not been on chemotherapy.

Oral androgen signaling inhibitor

They found that compared to patients receiving the same therapy for prostate cancer without pre-existing 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 pre-existing cardiovascular conditions is associate with roughly a 50% increase in mortality.