Does Relugolix Reduce Testosterone Levels in Men With Advanced Prostate Cancer?
Posted: Monday, June 22, 2020
Patients with advanced prostate cancer may achieve rapid, sustained androgen deprivation from treatment with relugolix, according to Bertrand Tombal, MD, PhD, of Cliniques Universitaires Saint Luc, Brussels, and colleagues. The findings of the multinational phase III HERO trial, which were published in The New England Journal of Medicine, suggested this oral gonadotropin-releasing hormone antagonist may outperform standard injectable hormone agonist therapies.
“Injectable luteinizing hormone–releasing hormone agonists are the standard agents for achieving androgen deprivation for prostate cancer despite the initial testosterone surge and delay in therapeutic effect,” the investigators commented. “Relugolix was developed as an oral, highly selective, gonadotropin-releasing hormone antagonist that…rapidly inhibits pituitary release of luteinizing hormone and follicle-stimulating hormone.”
In a 2:1 ratio, patients with advanced prostate cancer were randomly assigned to receive either relugolix (n = 622) or leuprolide (n = 308) for 48 weeks. Sustained testosterone suppression to castrate levels through 48 weeks was the primary endpoint. The study had three secondary endpoints: noninferiority with respect to the primary endpoint, castrate levels of testosterone on day 4, and profound castrate levels. A subgroup was evaluated for testosterone recovery (n = 184).
The primary endpoint was met, with 96.7% of patients in the relugolix group and 88.8% of patients in the leuprolide group maintaining castration through 48 weeks. Relugolix exhibited both superiority (P < .001) and noninferiority to leuprolide. According to the investigators, relugolix demonstrated superiority over leuprolide in all key secondary endpoints (P < .001). On day 4, 56% of the relugolix group achieved castrate levels of testosterone, compared with 0% of the leuprolide group. Subgroup analyses revealed higher mean testosterone levels 90 days after treatment discontinuation in the relugolix group than in the leuprolide group (288.4 ng/dL vs. 58.6 ng/dL). The investigators reported major adverse cardiovascular events in 2.9% versus 6.2% of patients in the relugolix and leuprolide groups, respectively.
Disclosure: For full disclosures of the study authors, visit nejm.org.