Androgen receptor signaling inhibitors linked to increased risk of cardiovascular adverse events in prostate cancer

Abstract

Men with advanced prostate cancer treated with the addition of androgen receptor signaling inhibitors (ARSIs) to traditional treatment with androgen deprivation therapy (ADT) have a 2-fold increased risk of developing an adverse cardiovascular (CV) event compared with those receiving ADT treatment alone according to the results of a meta-analysis published in JAMA Oncology.¹

That risk increases to 4-fold for developing grade 3 or higher CV events when ARSI doublet therapy, specifically abiraterone acetate and enzalutamide, is added to ADT. These risk increases were seen across the full spectrum of advanced prostate cancer, from nonmetastatic hormone-sensitive disease through metastatic castrate-resistant disease.

“The addition of androgen receptor signaling inhibitors to conventional hormone therapy has dramatically improved survival for prostate cancer patients,” says the senior author of the study, Ashwin Sachdeva, MBBS, PhD, National Institute for Health and Care Research Academic Clinical Lecturer in Urology at the University of Manchester. “However, we found that these treatments may also increase the risk of cardiovascular events.”

The meta-analysis included 24 studies of more than 22,000 patients with advanced prostate cancer treated with ADT intensification with ARSIs (abiraterone, apalutamide, darolutamide, and enzalutamide).

Secondary analyses showed that ARSIs also were linked to an increased risk of grade 3 or higher hypertension, cardiac dysrhythmia, and cerebrovascular events as well as a 2-fold increased risk of CV-related death (i.e., a grade 5 CV event).

Dr Sachdeva says that the findings underscore the need for urologists and oncologists to counsel patients on the potential risks of ARSIs and to ensure that CV risk factors are closely monitored and optimized in conjunction with the wider interdisciplinary team (i.e., primary care physicians and cardio-oncologists) when appropriate. “Simple measures such as improved management of co-morbidities, such as hypertension and diabetes, and use of lifestyle interventions may potentially help mitigate such risks,” he says.

In an editorial accompanying the study, Katelyn M. Atkins, MD, PhD, a radiation oncologist, and Andriana P. Nikolova, MD, PhD, an assistant professor of cardiology, both at Cedars–Sinai Medical Center in Los Angeles, California, say that the findings are a “call to action” to the medical community and a challenge “to re-examine the current CV risk estimation models which omit active cancer and certain cancer therapeutics as potent CV risk modifiers.”² They urge physicians overseeing prostate cancer survivors who are receiving ARSIs and ADT therapies to spread awareness of the heightened CV risk in these patients and underscore that the risk can be mitigated through appropriate screening.

To that end, they recommend a baseline CV risk assessment, repeated annually, for patients with prostate cancer. For patients at a higher risk of CV disease (i.e., they are older than 60 years with a least one CV risk factor or are younger than 60 years with two or more CV risk factors or a strong family history of atherosclerotic CV disease), they recommend a comprehensive CV risk assessment and management by a team that includes cardiologists or cardio-oncologists.

They also recommend early and consistent implementation of guideline-directed CV risk mitigation strategies that include statin therapy, aggressive blood pressure control, a heart-healthy diet, and regular exercise.