PRONOUCE fails to resolve CV safety questions for GnRH antagonists, agonists
medwireNews: Slow recruitment and low event rates have led to early termination of the PRONOUNCE trial, which hoped to determine the relative cardiovascular safety of gonadotropin-releasing hormone (GnRH) antagonists and agonists in men with prostate cancer.
At the time of closure, the study showed no significant difference in the rate of 12-month major adverse cardiovascular events (MACE; death, myocardial infarction, or stroke) between the 275 men randomly assigned to receive the GnRH antagonist degarelix for 12 months and the 269 given the GnRH agonist leuprolide for the same duration.
But the total of 544 participants, who all had preexisting atherosclerotic cardiovascular disease, was short of the planned total of 900 participants, even though recruitment took place at 113 sites across 12 countries from 2016 to 2020.
This meant that the data analysis had “wide confidence intervals and low statistical power, and therefore, the relative cardiovascular safety of GnRH antagonists and agonists remains unresolved,” write Renato Lopes (Duke Clinical Research Institute, Durham, North Carolina, USA) and co-authors in Circulation.
Approximately half (49.8%) of study participants had localized prostate cancer, 26.3% had locally advanced disease, and 20.4% had metastatic disease.
Lopes and team report that 5.5% of patients in the degarelix group and 4.1% of those in the leuprolide group experienced a MACE during the 12-month treatment period, a nonsignificant difference.
There was also no significant difference between the degarelix and leuprolide arms when unstable angina was included in the definition of MACE, with incidence at 6.2% and 5.6%, respectively.
Nor was there a difference in disease progression rates, occurring among 8.7% of men who received degarelix and 10.0% of those who received leuprolide.
Finally, the researchers found no difference between the two treatment arms in the incidence of severe adverse events (21.5% with degarelix vs 20.4% with leuprolide) or treatment discontinuation (4.7 vs 4.1%).
Lopes et al conclude that although the PRONOUNCE trial was terminated early, its prospective design “provides a model for the interdisciplinary collaboration between urologists, oncologists and cardiologists with a shared goal of evaluating the impact of cancer therapies on cardiovascular outcomes.”
The study findings were also presented as an abstract at the European Society of Cardiology Congress 2021.
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