Abiraterone acetate and enzalutamide are oral androgen signaling inhibitor therapies used in the treatment of patients with advanced prostate cancer. However, because elderly patients with prostate cancer who also have cardiovascular disease are often excluded from clinical trials, little has been known about the effect of these therapies on the clinical outcomes of these patients. In this interview with i3 Health, Grace Lu-Yao, PhD, MPH, discusses the increased mortality and hospitalization risk that she and colleagues have observed in elderly patients with advanced prostate cancer and cardiovascular disease treated with oral androgen inhibitors.
Can you comment on the significance of your study's results concerning the increased mortality and hospitalization risk for elderly patients with advanced prostate cancer and cardiovascular disease receiving oral androgen inhibitors?
Grace Lu-Yao, PhD, MPH: In our study, we found that patients who have at least three cardiovascular conditions experience significantly higher mortality. In fact, the patients who did not receive chemotherapy—that is, those who are in an earlier stage— experienced about a 56% increase in mortality within six months, which is quite significant. Most patients who have a cardiovascular condition have more than one; they usually have two or three. They may have atrial fibrillation, they may have acute myocardial infarction, or they may have other ischemic heart diseases. A patient with three conditions is at a much higher mortality risk, and most of the difference actually occurs within six months of treatment.
Were any of your findings surprising to you?
Dr. Lu-Yao: The most surprising finding is that we didn't see an increase in post-treatment hospitalization among patients receiving enzalutamide, but there was a substantial increase for abiraterone patients. This is surprising because the patients treated with abiraterone and enzalutamide had similar outcomes in mortality. The increase in hospitalization was actually quite substantial, about 55% on average for abiraterone. These patients are in a similar kind of stage window and there's really no guidance in terms of which patients should get abiraterone versus enzalutamide. I was surprised to see the big difference in post-term hospitalization. We all know hospitalizations are very expensive and could be serious for patient quality of life.
To what do you attribute the increased risk of hospitalization among patients treated with abiraterone?
Dr. Lu-Yao: It could be drug-drug interaction. We know that there's a certain class of drugs that may interact with abiraterone, but it could also be drug-disease interaction. For patients who already have hypertension or high cholesterol or glucose levels, abiraterone can aggravate those conditions and make them even worse, maybe more so than just the enzalutamide. Abiraterone is associated with two to three times the risk of cadiotoxicities, whereas the risks for enzalutamide are much lower.
How do you think that these results will impact current clinical practice?
Given that there's really not much data from clinical trials regarding elderly patients with prostate cancer and cardiovascular comorbidities, because clinical trials usually just focus on relatively healthy patients, we don't really know a lot. I think this is just the beginning of making the patient and the doctor be more aware that if we are using the new medication for a patient not eligible for a clinical trial, we'll have to be more careful in terms of monitoring the risk. We will have to monitor whether the patient's blood pressure and glucose are stable or getting worse, monitor their potential risk, and then implement a preventive strategy to reduce that risk.
About Dr. Lu-Yao
Grace Lu-Yao, PhD, MPH, is the Associate Director of Population Science at Sidney Kimmel Cancer Center (SKCC) and the Vice Chair of Population Science and Medical Oncology at Thomas Jefferson University in Philadelphia. She is also a Research Professor at Jefferson College of Population Health and the Research Director of the Neu Center for Supportive Medicine and Cancer Survivorship at SKCC. Her research focus is on outcomes research, cancer epidemiology, and surveillance, screening, and treatment for 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
Transcript edited for clarity. Any views expressed above are the speaker's own and do not necessarily represent those of i3 Health.