PRONOUNCE: Relative cardiovascular safety of GnRH antagonists vs agonists still unresolved
The gonadotropin-releasing hormone (GnRH) antagonist degarelix and the GnRH agonist leuprolide appear to be similar in terms of the rate of cardiovascular events in a cohort of patients with prostate cancer, according to the results of the PRONOUNCE trial.
PRONOUNCE included 545 patients (median age 73 years) enrolled between 3 May 2016 to 16 April 2020 from 113 sites across 12 countries. These patients were randomized to receive either degarelix or leuprolide for 12 months.
At baseline, 49.8 percent of the patients had localized prostate cancer, 26.3 percent had locally advanced disease, and 20.4 percent had metastatic disease. Median testosterone level was 330 ng/dL, while median prostate-specific antigen level was 12.83 ng/dL.
Due to the slower enrolment and the fewer number of primary outcome events than projected, the trial was terminated early before the 900 planned participants were accrued.
The primary outcome of major adverse cardiovascular events (composite of death, myocardial infarction, or stroke) through 12 months occurred in 15 patients on degarelix and 11 patients on leuprolide (5.5 percent vs 4.1 percent, respectively). The difference was not statistically significant (hazard ratio, 1.28, 95 percent confidence interval, 0.59–2.79; p=0.53).
Nevertheless, PRONOUNCE presents a model for interdisciplinary collaboration among urologists, oncologists, and cardiologists aimed at evaluating the impact of cancer therapies on cardiovascular outcomes.
*A Trial Comparing Cardiovascular Safety of Degarelix Versus Leuprolide in Patients With Advanced Prostate Cancer and Cardiovascular Disease