(UPDATE) Degarelix (Injectable GnRH Antagonist)

Commentary by Sandy Srinivas, MD, Prostate Cancer Site Editor for JNCCN 360

Professor of Medicine, Stanford University Medical Center

Are there reasons to choose a luteinizing hormone-releasing hormone (LHRH) antagonist over an LHRH agonist as androgen-deprivation therapy? This remains a very relevant question based on the mechanism of action of these drugs. Although biologic effects such as fewer cardiovascular effects are one of the primary reasons to use antagonists, more studies are needed to confirm or refute these hypotheses. Degarelix is used by a small fraction of older patients with cardiac comorbidities who are willing to have a monthly injection.

DISCLOSURES

Dr. Srinivas has received institutional research support from AstraZeneca Pharmaceuticals, Bayer HealthCare, Bristol Myers Squibb Company, Clovis Oncology, Eisai, Exelixis, Genentech, Merck & Co., Pfizer, and Seattle Genetics and has served on a scientific advisory board or as a consultant or expert witness to AstraZeneca Pharmaceuticals, AVEO Pharmaceuticals, Bayer HealthCare, Bristol Myers Squibb Company, Eisai, Janssen Pharmaceutica Products, Merck & Co., Novartis Pharmaceuticals Corporation, and Seattle Genetics.

Since the original Spotlight for degarelix was posted on JNCCN 360 in March 2021, two additional studies have focused on its use in prostate cancer. The BLADE study demonstrated that patients treated with degarelix did not experience increases in lean body mass and serum lipids and may thus have a lower risk of cardiovascular events than those who receive LHRH (also known as GnRH or gonadotropin-releasing hormone) agonists. According to Berruti and colleagues, the role of follicle-stimulating hormone in influencing sarcopenic obesity after androgen-deprivation therapy warrants further investigation.¹

Despite this evidence supporting the cardiovascular protective effect of degarelix compared with GnRH agonists, the primary results of the multicenter PRONOUNCE trial revealed a numeric—but nonsignificant—difference in the incidence of major adverse cardiovascular events between patients treated with degarelix versus the LHRH agonist leuprolide. The study was terminated prematurely, and, thus, according to Lopes and colleagues, the relative cardiovascular safety of LHRH antagonists and agonists remains unresolved.²

References

1. Palumbo C, Antonelli A, Triggiani L, et al. Changes in body composition and lipid profile in prostate cancer patients without bone metastases given degarelix treatment: the BLADE prospective cohort study. Prostate Cancer Prostatic Dis 2021;24:852–859.
2. 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;144:1295–1307.