Cardiovascular Safety of Prostate Cancer Treatments Still Undecided

New research has found that the relative cardiovascular safety of different types of androgen deprivation therapy (ADT) for prostate cancer remains unresolved after the PRONOUNCE trial was terminated early.

ADT has been associated with heart disease and stroke, particularly in men with pre-existing cardiovascular disease. However, it is unclear whether this is driven by the method of androgen deprivation, and previous research has suggested that gonadotropin-releasing hormone (GnRH) antagonists may be associated with a preferable cardiovascular safety profile, according to the study.

The PRONOUNCE trial was the first randomized clinical trial to compare the cardiovascular safety of a GnRH antagonist versus GnRH agonist in patients with prostate cancer. Further, this was the first interdisciplinary, cardio-oncology outcomes-based trial that has involved close collaboration between urologists, oncologists, and cardiologists, according to the investigators.

The trial enrolled 900 men with prostate cancer and concomitant atherosclerotic cardiovascular disease, who were randomized 1:1 to the GnRH antagonist degarelix or the GnRH agonist leuprolide for 12 months. The primary outcome was the time to first occurrence of a major adverse cardiovascular event, also known as a composite of death, myocardial infarction, or stroke through 12 months.

Since enrollment was slower than anticipated, the trial was terminated prematurely with fewer than half of the planned 66 endpoint events in 545 randomized patients, according to the investigators.

At 12 months, the analysis of 545 men had no statistically significant difference in the rate of MACE was observed between patients treated with degarelix compared with those treated with leuprolide. Additionally, there were 15 and 11 primary endpoint events in the degarelix and leuprolide groups.

“PRONOUNCE 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 due to smaller than planned numbers of participants and events and no difference in MACE at one year between patients assigned to degarelix or leuprolide was observed,” said principal study investigator Renato Lopes of Duke University Medical Center, Durham, US, in a press release. “Thus, the relative cardiovascular safety of GnRH antagonists and agonists remains unresolved. There is an ongoing need to understand the cardiovascular effects of oncological treatments as cancer survivorship increases and competing non-cancer death becomes more likely.”

Lopes added that PRONOUNCE provides a model for the interdisciplinary collaboration between oncologists and cardiologists with a shared goal of evaluating the impact of cancer therapies on cardiovascular outcomes.

REFERENCE

Jury still out on cardiovascular safety of prostate cancer treatments. European Society of Cardiology. August 30, 2021. Accessed August 31, 2021. https://www.escardio.org/The-ESC/Press-Office/Press-releases/Jury-still-out-on-cardiovascular-safety-of-prostate-cancer-treatments