Abiraterone acetate and enzalutamide, two oral androgen signaling inhibitor therapies, have been found to increase mortality in elderly patients with advanced prostate cancer and pre-existing cardiovascular disease (CVD).
Many of the clinical trials which led to the approval of abiraterone acetate and enzalutamide for the treatment of advanced prostate cancer excluded elderly patients, defined as those age 65 and older, with cardiovascular comorbidities, such as congestive heart failure, atrial fibrillation, stroke, acute myocardial infarction, and ischemic heart disease. Therefore, little was known about the role that oral androgen inhibitors play in the clinical outcomes of these patients.
Researchers led by Grace Lu-Yao, PhD, MPH, Professor and Vice Chair of medical oncology at Thomas Jefferson University and Associate Director of population science at the Sidney Kimmel Cancer Center in Philadelphia, conducted a population-based study to determine the effect of oral androgen inhibitors in elderly patients with advanced prostate cancer and CVD. Using the Surveillance, Epidemiology, and End Results (SEER) database, the investigators examined the data of 2,845 patients who had been treated with abiraterone acetate and 1,031 patients who had been treated with enzalutamide.
Patients with one to two CVDs had a 16% higher six-month mortality compared with patients who did not have CVD. Additionally, patients with three or more CVDs who had received chemotherapy prior to using oral androgen inhibitors had a greater risk of six-month mortality compared with patients with three or more CVDs who had not received chemotherapy (43% vs 56%). The results were the same for patients who had been treated with abiraterone acetate and those who had been treated with enzalutamide.
Dr. Lu-Yao and colleagues also observed an increased rate of post-treatment hospitalization among patients with three or more CVDs who had received abiraterone acetate but not among those who had received enzalutamide. Among patients who had not received chemotherapy, enzalutamide was associated with a 41% lower hospitalization rate compared to abiraterone acetate.
"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," conclude Dr. Lu-Yao and colleagues in their study, now published in European Urology. "The outcomes of this study provide relevant data to facilitate patient-physician discussions about the risks and benefits of treatment for men with advanced prostate cancer."
For More Information
Lu-Yao G, Nikita N, Keith SW, et al (2019). Mortality and hospitalization risk following oral androgen signaling inhibitors among men with advanced prostate cancer by pre-existing cardiovascular comorbidities. Eur Urol. [Epub ahead of print] DOI:10.1016/j.eururo.2019.07.031
Image credit: Otis Brawley