Kenneth Quinto, William H. Crown, Joseph S. Ross, Charu Gandotra, Eric C. Polley, Sanket S. Dhruva, Nilay Shah, Alyssa Berkowitz, Joshua D. Wallach, Jeph Herrin, Yihong Deng, Timothy D. Lyon, Xiaoxi Yao, Peter A. Noseworthy, and Rozalina G. McCoy
Key Points Question Can real-world data regarding the use of degarelix and leuprolide be used to emulate the forthcoming PRONOUNCE trial, a phase 3b trial comparing the cardiovascular safety of degarelix vs leuprolide among patients with prostate cancer and cardiovascular disease? Findings In this cohort study of 2226 propensity score–matched men with prostate cancer taking degarelix or leuprolide, no significant difference was observed in the risk of a major adverse cardiovascular event. Meaning These findings suggest that real-world data are increasingly available and useful for medical product evaluation, including for emulating clinical trials to understand products’ use in clinical practice and the associated benefits and harms of treatment., This cohort study uses electronic health record and administrative claims data to emulate the ongoing PRONOUNCE trial, which compares the cardiovascular safety of degarelix and leuprolide in men with cardiovascular disease and advanced prostate cancer., Importance With a growing interest in the use of real-world evidence for regulatory decision-making, it is important to understand whether real-world data can be used to emulate the results of randomized clinical trials. Objective To use electronic health record and administrative claims data to emulate the ongoing PRONOUNCE trial (A Trial Comparing Cardiovascular Safety of Degarelix Versus Leuprolide in Patients With Advanced Prostate Cancer and Cardiovascular Disease). Design, Setting, and Participants This retrospective, propensity-matched cohort study included adult men with a diagnosis of prostate cancer and cardiovascular disease who initiated either degarelix or leuprolide between December 24, 2008, and June 30, 2019. Participants were commercially insured individuals and Medicare Advantage beneficiaries included in a large US administrative claims database. Exposures Degarelix or leuprolide. Main Outcomes and Measures The primary end point was time to first occurrence of a major adverse cardiovascular event (MACE), defined as death due to any cause, myocardial infarction, or stroke, analogous to the PRONOUNCE trial. Secondary end points were time to death due to any cause, myocardial infarction, stroke, and angina. Cox proportional hazards regression was used to evaluate primary and secondary end points. Results A total of 32 172 men initiated degarelix or leuprolide for prostate cancer; of them, 9490 (29.5%) had cardiovascular disease, and 7800 (24.2%) met the PRONOUNCE trial eligibility criteria and were included in this study. Overall, 165 participants (2.1%) were Asian, 1390 (17.8%) were Black, 663 (8.5%) were Hispanic, and 5258 (67.4%) were White. The mean (SD) age was 74.4 (7.4) years. Among 2226 propensity score–matched patients, no significant difference was observed in the risk of MACE for patients taking degarelix vs those taking leuprolide (10.18 vs 8.60 events per 100 person-years; hazard ratio [HR], 1.18; 95% CI, 0.86-1.61). Degarelix was associated with a higher risk of death from any cause (HR, 1.48; 95% CI, 1.01-2.18) but not of myocardial infarction (HR, 1.16; 95% CI, 0.60-2.25), stroke (HR, 0.92; 95% CI, 0.45-1.85), or angina (HR, 1.36; 95% CI, 0.43-4.27). Conclusions and Relevance In this emulation of a clinical trial of men with cardiovascular disease undergoing treatment for prostate cancer, degarelix was not associated with a lower risk of cardiovascular events than leuprolide. Comparison of these data with PRONOUNCE trial results, when published, will help enhance our understanding of the appropriate role of using real-world data to emulate clinical trials.