Use of degarelix, a gonadotropin-releasing hormone (GnRH) antagonist, is associated with lower short-term risks for death and cardiovascular events than GnRH agonists in patients with metastatic prostate cancer, according to investigators. 

Shahrokh F. Shariat, MD, of Vienna General Hospital in Vienna, Austria, and colleagues conducted a systematic review and meta-analysis of 8 randomized clinical trials published during 2008 to 2019 and comprising 1646 men treated with degarelix and 986 with a GnRH agonist (leuprorelin or goserelin). (Concomitant administration of bicalutamide with a GnRH agonist for flare suppression was given in 6 studies.)

GnRH antagonist use was associated with a significant 52% and 48% lower risk for all-cause mortality and cardiovascular events, respectively, compared with agonist use over approximately 3 to 12 months, the investigators reported in European Urology. The team found no significant differences in the risks for PSA progression or serious adverse events (AEs), such as liver enzyme elevation, hepatic failure, and urine retention, between groups. Low rates of musculoskeletal events and fracture precluded rigorous analysis of these AEs.

GnRH agonist use, in contrast, was associated with lower risks for injection site reactions (4.8% vs 38%). The study revealed no significant difference in fatigue rate between the GnRH antagonist and GnRH agonists.


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Overall, treatment-emerging AEs occurred significantly more frequently in the GnRH antagonist than agonist recipients (73% vs 68%), but the rate of serious AEs were nonsignificantly similar between the groups (9.8% vs 11%). A total of 6.5% of GnRH antagonist users and 5.9% of GnRH agonist users discontinued androgen deprivation therapy due to AEs.

This meta-analysis was limited by the short follow-up time of the trials that prevents definitive conclusions.

“These findings should be interpreted with caution owing to the short follow-up duration and assessment of cardiovascular events as secondary endpoints in the included trials,” Dr Shariat’s team stated. They noted that their data do provide clinicians with useful information for patient counseling about the potential benefits and risks of a GnRH antagonist and agonist.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

Reference

Abufaraj M, Iwata T, Kimura S, et al. Differential impact of gonadotropin-releasing hormone antagonist versus agonist on clinical safety and oncologic outcomes on patients with metastatic prostate cancer: A meta-analysis of randomized controlled trials [published online June 27, 2020]. Eur Urol. doi: 10.1016/j.eururo.2020.06.002