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Randomized Controlled Trial
. 2021 Oct 19;144(16):1295-1307.
doi: 10.1161/CIRCULATIONAHA.121.056810. Epub 2021 Aug 30.

Cardiovascular Safety of Degarelix Versus Leuprolide in Patients With Prostate Cancer: The Primary Results of the PRONOUNCE Randomized Trial

Renato D Lopes  1 , Celestia S Higano  2 , Susan F Slovin  3 , Adam J Nelson  1 , Robert Bigelow, Per S Sørensen  4 , Chiara Melloni  1   5 , Shaun G Goodman  6   7 , Christopher P Evans  8 , Jan Nilsson  9 , Deepak L Bhatt  10 , Noel W Clarke  11 , Tine K Olesen  4 , Belinda T Doyle-Olsen  4 , Henriette Kristensen  4 , Lauren Arney  1 , Matthew T Roe  1   12 , John H Alexander  1 ; PRONOUNCE Study Investigators
Collaborators, Affiliations
Randomized Controlled Trial

Cardiovascular Safety of Degarelix Versus Leuprolide in Patients With Prostate Cancer: The Primary Results of the PRONOUNCE Randomized Trial

Renato D Lopes et al. Circulation. .

Erratum in

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.

Keywords: agonists; atherosclerosis; cardiotoxicity; drug therapy; gonadotropin-releasing hormone; prostatic neoplasms.

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Figures

Figure 1.
Figure 1.
CONSORT diagram
Figure 2.
Figure 2.
Primary endpoint: Kaplan-Meier plot of time from randomization to first adjudicated MACE, by treatment group
Figure 3.
Figure 3.
Timing of MACE by treatment group
Figure 4.
Figure 4.
Kaplan-Meier plot of progression-free survival (PFS), time from randomization to PFS failure, by treatment group
Figure 5.
Figure 5.
Median measured values and interquartile ranges for testosterone
See this image and copyright information in PMC

Comment in

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