The trial, which was terminated early due to slow enrollment and low number of events, did not conclusively show whether different modes of a common treatment for prostate cancer were associated with different levels of cardiovascular risk.
A late-breaking clinical trial led by the DCRI and presented Monday at the European Society of Cardiology highlighted the importance of further research into the potential cardiovascular risk of therapies to treat prostate and other cancers. The trial’s results were published simultaneously in Circulation.
The PRONOUNCE trial was the first prospective international randomized clinical trial to rigorously compare the cardiovascular safety of a GnRH antagonist and a GnRH agonist in patients with prostate cancer. Both GnRH agonists and antagonists belong to a class of therapies called androgen deprivation therapy (ADT) that is used to treat approximately half of people with prostate cancer.
Agonists are the most commonly prescribed mode of ADT, with only 3 to 4 percent of patients being prescribed an antagonist. While previous observational studies have suggested ADT could be linked to significant cardiovascular risk, less is known about whether the different modes of ADT—agonist or antagonist—impact risk differently.
PRONOUNCE was conducted at 113 sites in 12 countries. Patients with prostate cancer and pre-existing atherosclerotic cardiovascular disease were randomized to either a GnRH agonist (leuprolide) or antagonist (degarelix). The primary outcome was adjudicated major adverse cardiovascular events over 12 months. DCRI led both the steering committee and clinical events classification for the study.
Ultimately, enrollment was suspended early due to slow enrollment and fewer than expected cardiovascular events. The composite endpoint of cardiovascular death, nonfatal MI, or nonfatal stroke occurred in nine patients in the degarelix group and seven in the leuprolide group (HR 1.20, 95% CI 0.45–3.23). Because of the small number of events, findings from the trial did not conclusively show whether the two groups differed in terms of cardiovascular risk.
“Atherosclerotic cardiovascular disease is the leading cause of death, other than cancer, in men with prostate cancer,” said Renato D. Lopes, MD, PhD, who presented the study results and served on the study’s steering committee. “New cancer agents have extended patients’ survival, yet some of these agents have significant potential cardiovascular toxicity, particularly in patients with prior cardiovascular disease. A systematic assessment of cardiovascular risk is important before initiating cancer treatments.”
“PRONOUNCE did not provide conclusive results, underscoring the need for further studies in this area,” said DCRI’s John Alexander, MD, MHS, chair of the steering committee. “Nonetheless, the PRONOUNCE trial provides an important model for interdisciplinary collaboration between oncologists, urologists, and cardiologists with a shared goal of evaluating the impact of cancer therapies on cardiovascular outcomes.”
DCRI’s Lauren Arney, RN, also contributed to this study, along with former DCRI faculty Chiara Melloni, MD, and Matthew Roe, MD, and former DCRI fellow Adam Nelson, MBBS.