Hot Line - Do GnRH antagonists have better CV safety than GnRH agonists for prostate cancer?

The use of androgen deprivation therapy for the treatment of prostate cancer may increase the risk of cardiovascular (CV) events, particularly among men with pre-existing cardiovascular disease (CVD),¹ but it is unknown if this is driven by the method of androgen deprivation.

In a Hot Line session today, Professor Renato Lopes (Duke University Medical Center, Durham, North Carolina, USA) discussed the results of the PRONOUNCE trial, the first prospective, randomised trial of a gonadotropin-releasing hormone (GnRH) antagonist vs. a GnRH agonist to examine adjudicated CV events as primary and secondary endpoints.

Patients with advanced prostate cancer and concomitant atherosclerotic CVD were randomised 1:1 to receive 12 months of treatment with the GnRH antagonist degarelix or the GnRH agonist leuprolide. The primary outcome was time to first occurrence of a major adverse CV event (MACE), defined as a composite of death, myocardial infarction or stroke over 12 months.

Enrolment was slower than anticipated and the trial was terminated prematurely. Altogether, 545 out of a planned total of 900 men were randomised and there were fewer than half of the planned 66 endpoint events. The mean age of patients was 73.2 years.

At 12 months, there was no difference in the incidence of MACE between the degarelix group and the leuprolide group (5.5% vs. 4.1%; p=0.53).

In view of the inconclusive results, Prof. Lopes commented, “The relative CV safety of GnRH antagonists and agonists remains unresolved. There is an ongoing need to understand the CV effects of oncological treatments as cancer survivorship increases and competing non-cancer death becomes more likely.”

On a positive note, he remarked on the fact that the trial was the first multinational cardio-oncology outcomes-based trial involving close collaboration between different therapeutic specialties: “PRONOUNCE provides a model for the interdisciplinary collaboration between oncologists and cardiologists with a shared goal of evaluating the impact of cancer therapies on CV outcomes.”

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