MP48-04: Evaluating Cardiovascular Risk in Men Starting Androgen Deprivation Therapy for Prostate Cancer

Benjamin Lowentritt*, Towson, MD, Mark Fallick, Robert Dufour, Janis Pruett, Brisbane, CA, Tao Jiang, Boston, MA, Esmond Nwokeji, New York, NY, Mitch Nagao, Brisbane, CA

Introduction: Androgen Deprivation Therapy (ADT) remains the foundation of advanced prostate cancer (PC) treatment. Since 2010, the FDA has required warnings for risk of cardiovascular (CV) disease in labeling of Gonadotropin-Releasing Hormone (GnRH) receptor agonists. In 2021, the American Heart Association recommended baseline assessment of CV risk in men starting ADT. However, optimal evaluation and management of CV risks remain to be defined. This real-world study evaluated men receiving ADT for PC to understand the association between CV risk factors and future events.

Methods: Using a US claims dataset, men diagnosed with PC and receiving ADT between 2010-2019 were identified. Index date was first ADT claim. Continuous enrollment of =12 pre- and =6 months post-index was required. Qualifying CV events were post-index hospital admission or emergency department visit with ICD-9/10 or CPT codes for either a cerebrovascular accident, coronary bypass graft, myocardial infarction, percutaneous coronary intervention, thrombosis, and/or unstable angina. A Cox regression model including pre-index covariates of age, CV history, radiation or PC surgery, or other metastatic drug therapy, and time on GnRH agonist was used to examine time to first CV event up to 3 years post-index. Additionally, CV risk based on comorbidities and CV-related treatments were evaluated by groupings of high, moderate, and low risk scores.

Results: Of 10,530 men with PC treated with ADT, 10,008 (95.5%) received a GnRH agonist during the 3-year observation period and 899 (8.98%) experienced a CV event post-index. The Cox model showed that CV history (HR=2.80, p<0.0001, [95% Confidence Interval (CI):2.37 - 3.31]), high and moderate CV risk (vs low) (1.94, p<0.0001, [1.54 – 2.45] and 1.40, p<0.0049, [1.11 – 1.76], respectively), other metastatic drug therapy (1.62, p<0.001,[1.22 – 2.16]), time on GnRH agonist (1.05, p<0.0001, [1.02 – 1.07]) and age (1.06, p=0.04,[1.00-1.12]) were associated with higher risk for a CV event. Radiation or PC surgery was associated with lower risk of a CV event (HR=0.69, p<0.001, [95% CI: 0.57 – 0.84]).

Conclusions: In this study, CV history conveyed the highest risk of a new CV event up to 3 years after starting ADT treatment. Stratification by risk level was predictive of a CV event. Evaluation of these factors provides a framework for physicians starting men on ADT to identify those at greatest risk of CV events.

Source of Funding: Myovant Sciences GmbH, in collaboration with Pfizer.