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

Introduction: Abiraterone and enzalutamide are both approved in the United States for the treatment of metastatic castration-resistant prostate cancer (mCRPC). The objective of this study was to compare the real-world effectiveness and cardiovascular safety of these agents, drawing from a cohort of older adult patients diagnosed with mCRPC.

Materials and methods: The Surveillance, Epidemiology, and End Results-Medicare database was used to conduct an observational study comparing three-year overall survival and one-year risk of major adverse cardiovascular events (MACE) between initiators of abiraterone or enzalutamide between September 2012 and June 2017. Inverse-probability-of-treatment weighting was used to balance measured confounders. MACE was defined as a hospitalization for myocardial infarction, heart failure, or ischemic event (stroke or transient attack). Results were additionally stratified by levels of a claims frailty index (robust, prefrail, frail) and the presence of baseline cardiovascular comorbidities.

Results: The study population consisted of 4622 male adults 66 years of age and older diagnosed with mCRPC, of which 2430 initiated abiraterone and 2192 enzalutamide. The adjusted three-year overall survival was lower in patients initiating abiraterone (27.9 %) than enzalutamide (31.5 %) (adjusted survival difference [aSD] = -3.6 %, 95 % CI: -6.2 %, -0.9 %). In frailty-stratified analysis, no survival difference was found for the robust (aSD = 0.6 %, 95 % CI: -5.0 %, 6.3 %) or frail (aSD = -1.2 %, 95 % CI: -6.1 %, 3.7 %) subgroups, but there was lower survival with abiraterone for the prefrail group (aSD = -5.9 %, 95 % CI: -9.6, -2.3). The adjusted one-year risk of MACE was higher in abiraterone initiators (5.5 %) than enzalutamide initiators (3.6 %) (adjusted risk difference [aRD] = 1.8 %, 95 % CI: 0.6 %, 3.1 %); the increase was significant in the frail (aRD = 4.8 %, 95 % CI = 1.4 %, 8.3 %) and pre-frail subgroups (aRD =1.9 %, 95 % CI: 0.1 %, 3.6 %) but not the robust subgroup (aRD = -0.3 %, 95 % CI: -1.8 %, 1.2 %).

Discussion: The three-year survival of abiraterone initiators was slightly lower than that of enzalutamide initiators, though the agents showed similar survival for patients with robust fitness. A one-year increase in MACE risk was observed in abiraterone initiators, especially amongst frail individuals, highlighting the importance of assessing frailty during therapy selection.