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

Abstract

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.