Cardiovascular Safety of Degarelix Versus Leuprolide in Patients With Prostate Cancer: The Primary Results of the PRONOUNCE Randomized Trial
Authors: Lopes Renato D. , Higano Celestia S. , Slovin Susan F. , Nelson Adam J. , Bigelow Robert , Sørensen Per S. , Melloni Chiara , Goodman Shaun G. , Evans Christopher P. , Nilsson Jan , Bhatt Deepak L. , Clarke Noel W. , Olesen Tine K. , Doyle-Olsen Belinda T. , Kristensen Henriette , Arney Lauren , Roe Matthew T. , Alexander John H. , Mol-Arts Mirjam , Mansor-Lefebvre Samreen , Zubovskiy Konstantin , Blemings Allan , Dugi Klaus , Bloomfield Gerald , Kontos Chris , DeVore Adam , Jordan Dedrick , Kolls Bradley , Matthews Robin , Mehta Rajendra , Povsic Thomas J. , Morse Michael , Mahaffey Kenneth W. , Halabi Susan , Leong Darryl , Klotz Laurence , Fleshner Neil , Jansz Godfrey , Giddens Jonathan , Egerdie Russell , Chin Joseph , Zadra Joseph , Casey Richard , Simard Jean , Niazi Tamim , Martin André-Guy , Babjuk Marek , Hajek Jaroslav , Klecka Jiri , Kubes Jiri , Schraml Jan , Jakesova Jitka , Vanasek Jaroslav , Melichar Bohuslav , Seikkula Heikki , Abdiche Manouar Samir , Colombel Marc , Debourdeau Philippe , Robert Gregoire , Villers Arnauld , Ploussard Guillaume , Pradere Benjamin , Bruyere Franck , Descotes Jean-Luc , Ouzaid Idir , Winter Alexander , Hanitzsch Herbert , Sperling Herbert , Eckert Ralf , Hammerer Peter , Stagge Elke , Seseke Florian , Szymula Silvio , Bamias Aristotelis , Thanos Anastasios , Hatzimouratidis Konstantinos , Mamoulakis Charalambos , Kalofonos Haralabos , Oszukowska Elzbieta , Madziarska Katarzyna , Fijuth Jacek , Obarzanowski Mateusz , Alekseev Boris , Atduev Vagif , Pushkar Dmitri , Veliev Evgeniy , Zyryanov Alexander , Petrov Sergey , Kopyltsov Evgeny , Kozlov Vadim , Macko Ladislav , Dubravicky Jozef , Polak Richard , Mir Obaidullah , Vargovcak Marek , Mincik Ivan , Kliment Jan , Goncalves Frederico , Mikulas Juraj , Sokol Roman , Korcek Michal , Marko Jozef , Kovacik Viktor , Milichovsky Igor , Dubinsky Pavol , Lazarus John , Dixit Sanjay , Green Euan , Srinivasan Rajaguru , Mazhar Danish , Ng Yeung , Sarwar Naveed , Herman Craig , Snoy Frederick , Given Robert , Suh Ronald , Lipsitz David , Bailen James , Gervasi Lawrence , Acosta Idalia , Belkoff Laurence , Wu Ning , Frankel Jeffrey , Karsh Lawrence , Poole Bryant , Lieber David , Engel Jason , Bidair Mohamed , Rosenberg Steven , Sieber Paul , Perzin Adam , Kalota Susan , Singh Amar , Henderson Ralph , Wayne Jeffrey , Mirza Moben , D’Anna Richard , Wolk Fredrick , Padron Osvaldo , Bylow Kathryn , Rubenstein Jonathan , Gartrell Benjamin , Schwartz Michael , Patel Kalpesh , Maniam Ajit , Keane Thomas , Goodman Michael , Bane Charles , Chung Michael , Savage Stephen , Uchio Edward , Nguyen Son , Aronson William , Khanna Rakesh , Barnswell Carlton 
Published: August 2021

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.