Certain Prostate Cancer Therapies Increase Risks for Patients with Pre-existing Heart Disease

The effect of oral androgen signaling inhibitor therapies on patients with pre-existing cardiovascular disease may increase the risk of death.

Oral androgen signaling inhibitor therapies may increase the risk of death in patients with pre-existing cardiovascular disease (CVDs), according to a new study published in European Urology.

Androgen signaling inhibitors, such as abiraterone acetate and enzalutamide, are typically used to treat men with advanced prostate cancer that progressed on androgen deprivation therapy (ADT). Because previous clinical trials have excluded patients with multiple cardiovascular comorbidities, little is known about the effects of these medications on this patient population.

For the study, the researchers examined data from 3876 patients with advanced prostate cancer from the Surveillance, Epidemiology, and End Results (SEER) database. Of these patients, 67% of the men treated with abiraterone acetate or enzalutamide had at least 1 pre-existing cardiovascular condition in addition to prostate cancer.

According to the results, having 1 to 2 pre-existing CVDs was associated with a 16% higher 6-month mortality rate. Furthermore, this risk continued to increase among those having 3 or more CVDs, with a 43% increase in the relative risk of mortality with prior chemotherapy use and a 56% increase among those without documented chemotherapy use.

The researchers also analyzed changes in hospitalization rates following the use of oral androgen inhibitors. In patients with no history of chemotherapy, abiraterone acetate was associated with an increase in post-treatment hospitalization; however, this pattern was not observed in patients treated with enzalutamide. Compared with abiraterone acetate, enzalutamide resulted in a 41% lower post-treatment hospitalization rate among patients with at least 3 pre-existing CVDs and no history of chemotherapy, according to the study.

The results showed that patients taking multiple classes of mediations in addition to abiraterone acetate experienced higher hospitalizations.

“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,” study author 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, said in a press release. “Further studies are warranted to understand the potential mechanisms underlying the observations.”

According to Dr Lu-Yao, the results help fill the knowledge gap on the clinical outcomes of men with pre-existing CVDs treated with these therapies. Overall, the data can help further guide treatment decisions regarding the risks and benefits of treatments for men with prostate cancer, according to the researchers.

“The findings bring home the importance in having multidisciplinary teams weigh in on treatment decisions for cancer patients,” co-author Wm. Kevin Kelly, DO, professor of medical oncology and director of solid tumor oncology at the Sidney Kimmel Cancer Center — Jefferson Health, concluded.

References

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. European Urology. 2019. Doi: https://doi.org/10.1016/j.eururo.2019.07.031

Risks for Patients with Pre-existing Conditions on Novel Prostate Cancer Therapies [news release]. Jefferson Health. https://www.jefferson.edu/about/news-and-events/2019/8/risks-of-novel-hormone-prostate-cancer-therapy-and-pre-existing-conditions.html. Accessed August 13, 2019.