Renato D Lopes1, Celestia S Higano2, Susan F Slovin3, Adam J Nelson1, Robert Bigelow, Per S Sørensen4, Chiara Melloni1,5, Shaun G Goodman6,7, Christopher P Evans8, Jan Nilsson9, Deepak L Bhatt10, Noel W Clarke11, Tine K Olesen4, Belinda T Doyle-Olsen4, Henriette Kristensen4, Lauren Arney1, Matthew T Roe1,12, John H Alexander1. 1. Department of Medicine, Division of Cardiology, Duke Clinical Research Institute, Duke University Medical Center, Durham, NC (R.D.L., A.J.N., C.M., L.A., M.T.R., J.H.A.). 2. Division of Medical Oncology, University of Washington and Fred Hutchinson Cancer Research Center, Seattle (C.S.H.). 3. Genitourinary Oncology Service, Department of Medicine, Sidney Kimmel Center for Prostate and Urologic Cancers, Memorial Sloan Kettering Cancer Center, New York, NY (S.F.S.). 4. Ferring Pharmaceuticals A/S, Copenhagen, Denmark (P.S.S., T.K.O., B.T.D.-O., H.K.). 5. IQVIA, Durham, NC (C.M.). 6. Division of Cardiology, St. Michael's Hospital, Department of Medicine, University of Toronto, Ontario, Canada (S.G.G.). 7. Canadian VIGOUR Centre, University of Alberta, Edmonton, Canada (S.G.G.). 8. Department of Urologic Surgery, University of California, Davis, Sacramento (C.P.E.). 9. Department of Clinical Sciences Malmö, Lund University, Sweden (J.N.). 10. Division of Cardiovascular Medicine, Brigham and Women's Hospital Heart and Vascular Center, Harvard Medical School, Boston, MA (D.L.B.). 11. Department of Urology, The Christie and Salford Royal Hospitals Manchester, United Kingdom (N.W.C.). 12. Verana Health, San Francisco, CA (M.T.R.).
Abstract
BACKGROUND: The relative cardiovascular safety of gonadotropin-releasing hormone (GnRH) antagonists compared with GnRH agonists in men with prostate cancer and known atherosclerotic cardiovascular disease remains controversial. METHODS: In this international, multicenter, prospective, randomized, open-label trial, men with prostate cancer and concomitant atherosclerotic cardiovascular disease were randomly assigned 1:1 to receive the GnRH antagonist degarelix or the GnRH agonist leuprolide for 12 months. The primary outcome was the time to first adjudicated major adverse cardiovascular event (composite of death, myocardial infarction, or stroke) through 12 months. RESULTS: Because of slower-than-projected enrollment and fewer-than-projected primary outcome events, enrollment was stopped before the 900 planned participants were accrued. From May 3, 2016, to April 16, 2020, a total of 545 patients from 113 sites across 12 countries were randomly selected. Baseline characteristics were balanced between study groups. The median age was 73 years, 49.8% had localized prostate cancer; 26.3% had locally advanced disease, and 20.4% had metastatic disease. A major adverse cardiovascular event occurred in 15 (5.5%) patients assigned to degarelix and 11 (4.1%) patients assigned to leuprolide (hazard ratio, 1.28 [95% CI, 0.59-2.79]; P=0.53). CONCLUSIONS: PRONOUNCE (A Trial Comparing Cardiovascular Safety of Degarelix Versus Leuprolide in Patients With Advanced Prostate Cancer and Cardiovascular Disease) is the first, international, randomized clinical trial to prospectively compare the cardiovascular safety of a GnRH antagonist and a GnRH agonist in patients with prostate cancer. The study was terminated prematurely because of the smaller than planned number of participants and events, and no difference in major adverse cardiovascular events at 1 year between patients assigned to degarelix or leuprolide was observed. The relative cardiovascular safety of GnRH antagonists and agonists remains unresolved. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02663908.
BACKGROUND: The relative cardiovascular safety of gonadotropin-releasing hormone (GnRH) antagonists compared with GnRH agonists in men with prostate cancer and known atherosclerotic cardiovascular disease remains controversial. METHODS: In this international, multicenter, prospective, randomized, open-label trial, men with prostate cancer and concomitant atherosclerotic cardiovascular disease were randomly assigned 1:1 to receive the GnRH antagonist degarelix or the GnRH agonist leuprolide for 12 months. The primary outcome was the time to first adjudicated major adverse cardiovascular event (composite of death, myocardial infarction, or stroke) through 12 months. RESULTS: Because of slower-than-projected enrollment and fewer-than-projected primary outcome events, enrollment was stopped before the 900 planned participants were accrued. From May 3, 2016, to April 16, 2020, a total of 545 patients from 113 sites across 12 countries were randomly selected. Baseline characteristics were balanced between study groups. The median age was 73 years, 49.8% had localized prostate cancer; 26.3% had locally advanced disease, and 20.4% had metastatic disease. A major adverse cardiovascular event occurred in 15 (5.5%) patients assigned to degarelix and 11 (4.1%) patients assigned to leuprolide (hazard ratio, 1.28 [95% CI, 0.59-2.79]; P=0.53). CONCLUSIONS: PRONOUNCE (A Trial Comparing Cardiovascular Safety of Degarelix Versus Leuprolide in Patients With Advanced Prostate Cancer and Cardiovascular Disease) is the first, international, randomized clinical trial to prospectively compare the cardiovascular safety of a GnRH antagonist and a GnRH agonist in patients with prostate cancer. The study was terminated prematurely because of the smaller than planned number of participants and events, and no difference in major adverse cardiovascular events at 1 year between patients assigned to degarelix or leuprolide was observed. The relative cardiovascular safety of GnRH antagonists and agonists remains unresolved. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02663908.
Entities:
Keywords:
agonists; atherosclerosis; cardiotoxicity; drug therapy; gonadotropin-releasing hormone; prostatic neoplasms
Authors: Behfar Ehdaie; Coral L Atoria; Amit Gupta; Andrew Feifer; William T Lowrance; Michael J Morris; Peter T Scardino; James A Eastham; Elena B Elkin Journal: Cancer Date: 2011-11-09 Impact factor: 6.860
Authors: Kathleen M Sturgeon; Lei Deng; Shirley M Bluethmann; Shouhao Zhou; Daniel M Trifiletti; Changchuan Jiang; Scott P Kelly; Nicholas G Zaorsky Journal: Eur Heart J Date: 2019-12-21 Impact factor: 29.983
Authors: Glenn N Levine; Anthony V D'Amico; Peter Berger; Peter E Clark; Robert H Eckel; Nancy L Keating; Richard V Milani; Arthur I Sagalowsky; Matthew R Smith; Neil Zakai Journal: Circulation Date: 2010-02-01 Impact factor: 29.690
Authors: Neal D Shore; Fred Saad; Michael S Cookson; Daniel J George; Daniel R Saltzstein; Ronald Tutrone; Hideyuki Akaza; Alberto Bossi; David F van Veenhuyzen; Bryan Selby; Xiaolin Fan; Vicky Kang; Jackie Walling; Bertrand Tombal Journal: N Engl J Med Date: 2020-05-29 Impact factor: 91.245
Authors: Christopher J Sweeney; Yu-Hui Chen; Michael Carducci; Glenn Liu; David F Jarrard; Mario Eisenberger; Yu-Ning Wong; Noah Hahn; Manish Kohli; Matthew M Cooney; Robert Dreicer; Nicholas J Vogelzang; Joel Picus; Daniel Shevrin; Maha Hussain; Jorge A Garcia; Robert S DiPaola Journal: N Engl J Med Date: 2015-08-05 Impact factor: 91.245
Authors: Andrea Kokorovic; Alan I So; Hosam Serag; Christopher French; Robert J Hamilton; Jason P Izard; Jasmir G Nayak; Frédéric Pouliot; Fred Saad; Bobby Shayegan; Armen Aprikian; Ricardo A Rendon Journal: Can Urol Assoc J Date: 2022-08 Impact factor: 2.052
Authors: Andrea Kokorovic; Alan I So; Hosam Serag; Christopher French; Robert J Hamilton; Jason P Izard; Jasmir G Nayak; Frédéric Pouliot; Fred Saad; Bobby Shayegan; Armen Aprikian; Ricardo A Rendon Journal: Can Urol Assoc J Date: 2022-08 Impact factor: 2.052
Authors: Avirup Guha; Yan Gong; David DeRemer; Jocelyn Owusu-Guha; Susan F Dent; Richard K Cheng; Neal L Weintraub; Neeraj Agarwal; Michael G Fradley Journal: J Cardiovasc Pharmacol Date: 2022-10-01 Impact factor: 3.271
Authors: Jutta Bergler-Klein; Peter P Rainer; Markus Wallner; Marc-Michael Zaruba; Jakob Dörler; Armin Böhmer; Tamara Buchacher; Maria Frey; Christopher Adlbrecht; Rupert Bartsch; Mariann Gyöngyösi; Ursula-Maria Fürst Journal: Wien Klin Wochenschr Date: 2022-05-04 Impact factor: 2.275
Authors: David Merola; Sebastian Schneeweiss; Sushama K Sreedhara; Luke E Zabotka; Kenneth Quinto; John Concato; Shirley V Wang Journal: JNCI Cancer Spectr Date: 2022-08-10