Real-world comparative effectiveness and cardiovascular safety of enzalutamide versus abiraterone amongst older men diagnosed with metastatic castration-resistant prostate cancer.

5053 Background: Abiraterone and enzalutamide are frequently used in treating metastatic castration-resistant prostate cancer (mCRPC), and their use has expanded to castration-sensitive and non-metastatic settings. The objective of this study was to compare real-world overall survival and risk of major adverse cardiovascular events (MACE) between initiators of abiraterone and enzalutamide in a cohort of older adult men with mCRPC. Methods: The Surveillance Epidemiology and End Results-Medicare database was leveraged to design a comparative observational study. Initiators of abiraterone or enzalutamide between 2011-2017 were identified, a period when both drugs were only approved for mCRPC. Propensity scores and inverse-probability-of-treatment weighting were used to balance measured confounders. MACE was defined as a hospitalization for myocardial infarction, heart failure, or ischemic stroke or transient ischemic attack. Hazard ratios were obtained from weighted Cox proportional hazards (mortality) and Fine-and-Gray models (MACE). Results: The study population consisted of 5,633 men 66 years of age and older diagnosed with mCRPC, of which 3,720 initiated abiraterone and 1,913 enzalutamide. The median age at initiation was 77. Compared to enzalutamide initiators, the overall survival was similar in patients initiating abiraterone at both one-year (mortality hazard ratio (HR) = 1.05; 95% CI: 0.95 – 1.17) and five-years of follow up (HR= 1.01; 95% CI: 0.95 – 1.08). The one-year risk of MACE was higher in abiraterone initiators (HR = 1.30; 95% CI: 1.01 – 1.67). The agents displayed similar effects on MACE when considering a five-year follow-up period after therapy initiation (Table). Conclusions: The long-term comparative effectiveness and cardiovascular safety of abiraterone and enzalutamide were similar, though a short-term increase in MACE was seen in abiraterone initiators, highlighting the importance of considering cardiovascular risk and cancer prognosis during therapy selection.[Table: see text]