TY - JOUR
T1 - Real-world Cardiovascular Outcomes Associated with Degarelix vs Leuprolide for Prostate Cancer Treatment
AU - Wallach, Joshua D.
AU - Deng, Yihong
AU - McCoy, Rozalina G.
AU - Dhruva, Sanket S.
AU - Herrin, Jeph
AU - Berkowitz, Alyssa
AU - Polley, Eric C.
AU - Quinto, Kenneth
AU - Gandotra, Charu
AU - Crown, William
AU - Noseworthy, Peter
AU - Yao, Xiaoxi
AU - Shah, Nilay D.
AU - Ross, Joseph S.
AU - Lyon, Timothy D.
N1 - Funding Information:
Berkowitz, Polley, Quinto, Gandotra, Crown, Noseworthy, Yao, Shah, Ross, Lyon. Statistical analysis: Wallach, Deng, Herrin, Polley, Yao. Obtained funding: Shah, Ross. Administrative, technical, or material support: Berkowitz, Quinto, Crown, Noseworthy, Shah. Supervision: Noseworthy, Ross, Lyon. Conflict of Interest Disclosures: Dr Wallach reported receiving research support through the Collaboration for Research Integrity and Transparency (CRIT) at Yale University from the Laura and John Arnold Foundation and through the Yale–Mayo Clinic Center for Excellence in Regulatory Science and Innovation (CERSI) program (U01FD005938) and being supported by the National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health under award K01AA028258. Dr McCoy reported receiving support from the National Institute of Health National Institute of Diabetes and Digestive and Kidney Diseases under grant K23DK114497 and, in the past 36 months, receiving support from an AARP Quality Measure Innovation Grant, the Mayo Clinic Center for Health Equity and Community Engagement Research, and the Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery. Dr Dhruva reported being funded by the National Heart, Lung, and Blood Institute of the National Institutes of Health (K12HL138046), the National Evaluation System for Health Technology (NEST), the Greenwall Foundation, and Arnold Ventures. Dr Herrin reported working under contract to the Centers for Medicare & Medicaid Services on the development and evaluations of measures of health care quality. Dr Noseworthy reported receiving personal fees from Optum during the conduct of the study. Dr. Shah reported receiving support through the Mayo Clinic from the Food and Drug Administration to establish the Yale– Mayo Clinic CERSI program (U01FD005938); the Centers of Medicare & Medicaid Innovation under the Transforming Clinical Practice Initiative; the Agency for Healthcare Research and Quality (R01HS025164, R01HS025402, R03HS025517, and K12HS026379); the National Heart, Lung, and Blood Institute of the US National Institutes of Health (R56HL130496, R01HL131535, and R01HL151662); the National Science Foundation; and the Patient-Centered Outcomes Research Institute to develop a clinical data research network (LHSNet). Dr Ross reported that in the past 36 months, he has received support through Yale University from the Laura and John Arnold Foundation for CRIT at Yale, from Medtronic, Inc, and the Food and Drug Administration to develop
Funding Information:
Funding/Support: This publication is supported by the US Food and Drug Administration (FDA) of the US Department of Health and Human Services (HHS) as part of a financial assistance award U01FD005938 totaling $250,000 with 100% funded by FDA/HHS.
Publisher Copyright:
© 2021 Wallach JD et al.
PY - 2021/10/22
Y1 - 2021/10/22
N2 - 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 32172 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.
AB - 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 32172 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.
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U2 - 10.1001/jamanetworkopen.2021.30587
DO - 10.1001/jamanetworkopen.2021.30587
M3 - Article
AN - SCOPUS:85118135780
VL - 4
JO - JAMA network open
JF - JAMA network open
SN - 2574-3805
IS - 10
M1 - e2130587
ER -