A Trial Comparing Cardiovascular Safety of Degarelix Versus Leuprolide in Patients With Advanced Prostate Cancer and Cardiovascular Disease - PRONOUNCE

Aug 30, 2021
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Author/Summarized by Author:
Anthony A. Bavry, MD, MPH, FACC
Summary Reviewer:
Kim A. Eagle, MD, MACC
Trial Sponsor:
Ferring Pharmaceuticals
Date Presented:
08/30/2021
Date Published:
08/30/2021
Date Updated:
08/30/2021
Original Posted Date:
08/30/2021
References

Contribution To Literature:

The PRONOUNCE trial was terminated early; therefore, the relative cardiovascular safety of GnRH antagonists and agonists remains unknown.

Description:

The goal of the trial was to evaluate gonadotropin-releasing hormone (GnRH) antagonists compared with GnRH agonists among patients with prostate cancer. GnRH antagonists and GnRH agonists inhibit testosterone production, which is necessary for androgen deprivation therapy.

Study Design

  • Randomization
  • Parallel
  • Open-label
  • Stratification

Participants with prostate cancer were randomized to the GnRH antagonist degarelix (n = 275) versus the GnRH agonist leuprolide (n = 269).

Degarelix was given as a 240 mg subcutaneous dose followed by 11 maintenance doses of 80 mg injections every 28 days. Leuprolide was given as 5 mg intramuscular injection followed by three similar injections every 84 days.

  • Total number of enrollees: 545
  • Duration of follow-up: 12 months
  • Mean patient age: 73 years
  • Percentage female: 0
  • Percentage with diabetes: 32%

Inclusion criteria:

  • Patients with prostate cancer undergoing androgen deprivation therapy

Other salient features/characteristics:

  • 49.8%, localized prostate cancer
  • 26.3%, locally advanced disease
  • 20.4%, metastatic disease

Principal Findings:

The primary outcome, major adverse cardiovascular events, was 5.5% in the degarelix group compared with 4.1% in the leuprolide group (p = 0.53).

Secondary outcomes:

  • All-cause death: 2.9% with degarelix vs. 3.3% with leuprolide
  • Myocardial infarction: 1.8% with degarelix vs. 1.1% with leuprolide
  • Stroke: 1.1% with degarelix vs. 1.1% with leuprolide

Interpretation:

Among patients with prostate cancer, androgen deprivation therapy can be achieved with GnRH antagonists and agonists. Major adverse cardiovascular events were similar between the degarelix group compared with the leuprolide group; however, since this trial was terminated early, the relative cardiovascular safety of these agents remains unknown. This trial can serve as a template for how cardiologists and oncologists can cooperate on cardio-oncology trials in the future.

References:

Lopes RD, Higano CS, Slovin SF, et al. Cardiovascular Safety of Degarelix Versus Leuprolide in Patients With Prostate Cancer: The Primary Results of the PRONOUNCE Randomized Trial. Circulation 2021;Aug 30:[Epub ahead of print].

Presented by Dr. Renato Lopes at the European Society of Cardiology Virtual Congress, August 30, 2021.

Clinical Topics: Cardio-Oncology, Prevention

Keywords: ESC Congress, ESC21, Androgen Antagonists, Androgens, Cardiotoxicity, Gonadotropin-Releasing Hormone, Leuprolide, Myocardial Infarction, Neoplasms, Primary Prevention, Prostate, Prostatic Neoplasms, Stroke, Testosterone


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