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

Charles Gaber University of Illinois-Chicago, Chicago, IL info_outline Charles Gaber, Ebere Okpara, Abdullah Abdelaziz, Jyotirmoy Sarker, Kent Hanson, Lubna Hassan, Fang-Ju Lin, Todd Lee, Natalie Marie Reizine

Authors Charles Gaber University of Illinois-Chicago, Chicago, IL info_outline Charles Gaber, Ebere Okpara, Abdullah Abdelaziz, Jyotirmoy Sarker, Kent Hanson, Lubna Hassan, Fang-Ju Lin, Todd Lee, Natalie Marie Reizine Organizations University of Illinois-Chicago, Chicago, IL, University of Illinois at Chicago, Chicago, IL, University of Illinois- Chicago, Chicago, IL, National Taiwan University, Taipei, Taiwan, University of Illinois Chicago, Chicago, IL Abstract Disclosures Research Funding No funding sources reported 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. Outcomes in a propensity-score weighted population of older adult men diagnosed with mCRPC initiating abiraterone or enzalutamide between 2011-2017. Abiraterone (n = 3,720) Enzalutamide (n = 1,913) Measures of Contrast (Abiraterone vs. Enzalutamide) Percentage (95% CI) Percentage (95% CI) Percentage Point Difference (95% CI) HR (95% CI) Overall survival 1-year 67.1 (65.6, 68.7) 67.9 (65.7, 70.1) -0.8 (-3.5, 1.9) 1.05 (0.95, 1.17) 5-year 16.2 (15.0, 17.4) 16.0 (14.3, 17.8) 0.1 (-2.0, 2.3) 1.01 (0.95, 1.08) MACE risk 1-year 5.9 (5.1, 6.7) 4.5 (3.5, 5.4) 1.4 (0.2, 2.7) 1.30 (1.01, 1.67) 5-year 12.2 (11.0, 13.3) 12.6 (11.0, 14.3) -0.4 (-0.2, 1.5) 1.04 (0.88, 1.23) CI, confidence interval; HR, hazard ratio; MACE, major adverse cardiovascular event.