The phase 3 HERO trial recently demonstrated superior suppression of testosterone levels to castration with a new oral gonadotrophic-releasing hormone (GnRH) receptor antagonist relugolix compared to leuprolide with fewer major adverse cardiovascular events in men with advanced prostate cancer. In a poster presented during the 2021 American Society of Clinical Oncology Genitourinary Cancers Symposium, the investigators presented a subgroup analysis from the trial of 125 patients who received concomitant prostate cancer treatments showing relugolix maintained similar efficacy in this group.
Traditionally, testosterone suppression for the treatment of advanced prostate cancer is done through GnRH receptor agonists (also known as luteinizing hormone releasing hormone agonists) such as leuprolide, which is an injectable agent. Injectable GnRH receptor antagonists have more recently been introduced, with degarelix approved by the FDA in 2008. The potential advantage of GnRH receptor antagonists is quicker reduction of testosterone levels without an initial testosterone surge. However, the injectable degarelix has not been widely adopted, possibly due to injection site reactions and monthly injection requirements, whereas leuprolide can be given less frequently.
Relugolix represents a new oral option for GnRH receptor antagonism. In the study, Dr. Daniel J. George and colleagues report castration rates of 95.8% among patients receiving enzalutamide or docetaxel and 96.9% among patients receiving radiation therapy. The values were very similar to the rates among patients that did not simultaneously receive another therapy (96.7%). The overall proportion of patients receiving concomitant therapy in the HERO trial was small at 13.4% (n=125/934) due to included patient population, but the findings are notable as many patients with advanced prostate cancer may ultimately receive these additional therapies.
J Clin Oncol 39, 2021 (suppl 6; abstr 106)
Shore ND, Saad F, Cookson MS, et al. Oral Relugolix for Androgen-Deprivation Therapy in Advanced Prostate Cancer. N Engl J Med. 2020 Jun 4;382(23):2187-2196.