Androgen receptor inhibitor treatments: Cardiovascular adverse events and comorbidity considerations in patients with non-metastatic prostate cancer

Objectives: Prostate cancer and cardiovascular (CV) disease share several risk factors, with the incidence of both rising with increasing age. Systemic prostate cancer therapies may increase CV risk. For example, gonadotropic releasing hormone agonists have been associated with increased development of CV risk factors, and potentially with CV disease. For men with non-metastatic castration-resistant prostate cancer (nmCRPC), the opportunity to mitigate CV risk by appropriate selection of therapy (i.e., use of newer agents such as androgen receptor inhibitors) may be possible. The phase 3 PROSPER, SPARTAN, and ARAMIS trials for enzalutamide, apalutamide, and darolutamide, the 3 approved androgen receptor inhibitors for men with nmCRPC, were all associated with increased metastasis-free survival in patients with metastatic castration-resistant prostate cancer (mCRPC). Our objective in writing this review is to improve awareness of the relationship between long-term androgen deprivation and increased risk for CV disease and inform treatment decision making for patients with mCRPC who also have CV comorbidities.

Methods: The PubMed database was searched from 2010 to November 5, 2019 for articles pertaining to androgen receptor inhibitors, androgen inhibition, apalutamide, darolutamide, enzalutamide, CV, and CaP.

Results: We found literature describing the relationship between androgen inhibition and CV disease and risks. Given the increased risk of CV disease due to exposure to gonadotropic releasing hormone agonist therapy alone, understanding the potential for additional CV risks is important for patients with CV comorbidities when an androgen receptor inhibitor is added to their treatment. Another important consideration is the possibility of drug-drug interactions with comedications.

Conclusion: Management strategies for patients with mCRPC also treated for comorbidities including CV disease require appropriate selection of therapy, diet, and exercise to meet the needs of the individual patient profile.