Pre-existing cardiovascular disease (CVD) increases the short-term mortality risk among men taking the oral antiandrogens abiraterone or enzalutamide for advanced prostate cancer (PCa), a new population-based study suggests.
Compared with patients who had no pre-existing CVD, those with 1 or 2 pre-existing CVDs had a significant 16% increased risk of dying from any cause within 6 months of initiating treatment with abiraterone (AA) or enzalutamide (ENZ), Grace Lu-Yao, PhD, MPH, of the Sidney Kimmel Cancer Center at Jefferson in Philadelphia, and colleagues reported in European Urology. Patients with 3 or more CVDs had a significant 56% increased risk. In addition, AA or ENZ use was associated with an increased risk of hospitalization among men with pre-existing hypertension.
Dr Lu-Yao’s team noted that pivotal trials of AA excluded men with clinically significant CVD or serious coexisting nonmalignant disease, or uncontrolled hypertension; pivotal trials of ENZ excluded patients with significant comorbidities. Consequently, little is known about the effects of these drugs on these patients, according to the investigators.
“Our findings highlight the importance of conducting outcome evaluation among patients not meeting pivotal trial eligibility criteria in the real-world setting,” the investigators wrote.
Their findings should “spur clinicians to integrate this knowledge into their clinical decision making for patients with PCa and CVD.”
The study included 2845 men treated with abiraterone and 1031 treated with enzalutamide identified using the Surveillance, Epidemiology and End Results (SEER)-Medicare linked database. Of these patients, 67% had at least 1 pre-existing CVD. “A substantial portion of AA and ENZ users in the real-world setting had pre-existing CVDs and was unlikely to meet the eligibility criteria of clinical trials,” the authors stated.
Pre-existing CVDs included acute myocardial infarction, atrial fibrillation, congestive heart failure, stroke, and ischemic heart disease.
A major strength of the study was the use of data from a large, rich, population-based database with broad representation of various racial or ethnic groups treated in many different clinical settings, according to the investigators. Consequently, “the findings are likely to apply to a majority of patients.” Study limitations included its retrospective design, the inability to identify appropriate control patients not received AA or ENZ, and the potential for misclassification of comorbidities and unmeasured confounders, the investigators noted.
The authors pointed out that, during the study period, AA and ENZ were used primarily in patients with castration-resistant PCa. As result, these patients were more likely to have androgen deprivation therapy, which is associated with an increase in fat mass, a loss of muscle mass, changes in lipid balance, and an increased risk of metabolic syndrome. “This is a known contributor to CVDs and thus a likely contributor in the observed outcomes.”
Lu-Yao G, Nikita N, Keith SW, et al. Mortality and hospitalization risk following oral androgen signaling inhibitors among men with advanced prostate cancer by pre-existing cardiovascular comorbidities. Eur Urol. 2019. https://doi.org/10.1016/j.eururo.2019.07.031