The phase 3 HERO trial demonstrated superior suppression of testosterone levels to castrate levels with a first-in-class oral gonadotrophic-releasing hormone (GnRH) receptor antagonist, relugolix, compared with leuprolide, with fewer major adverse cardiovascular events in men with advanced prostate cancer. These data served as evidence for FDA approval of relugolix for treatment of advanced prostate cancer. In a poster presented during the 2021 ASCO Genitourinary Cancers Symposium, Dr. Daniel J. George (Duke Cancer Institute for Prostate and Urologic Cancer, Durham, NC) and colleagues presented a subgroup analysis from the trial of the 125 patients in the HERO trial who received concomitant prostate cancer treatments, showing that relugolix maintained similar efficacy in this group.
Traditionally, testosterone suppression for the treatment of advanced prostate cancer is achieved through GnRH receptor agonists (also known as luteinizing hormone releasing hormone [LHRH] agonists) such as leuprolide, which is an injectable agent. Injectable GnRH receptor antagonists have been available since 2008, when degarelix was approved by the FDA. The potential advantage of GnRH receptor antagonists is quicker reduction of testosterone levels without an initial testosterone surge. However 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 subgroup analysis, Dr. George and colleagues reported castration rates of 95.8% among patients who had received enzalutamide or docetaxel and 96.9% among patients who had undergone radiation therapy. The values were very similar to the rates among patients who did not simultaneously receive another therapy (96.7%). Although the overall proportion of patients who received concomitant therapy in the HERO trial was small, at 13.4% (n=125/934), due to inclusion criteria, the findings were notable, as many patients with advanced prostate cancer may ultimately receive these additional therapies.
Hiten D. Patel, MD, MPH, completed residency training in urologic surgery at the James Buchanan Brady Urological Institute and is currently a Clinical Instructor and Fellow in Urologic Oncology at Loyola University Medical Center. He has published studies related to epidemiology, comparative effectiveness, evidence-based reviews, and clinical trials in urologic oncology and related fields.
George DJ, Shore ND, Saad F, et al. Impact of concomitant prostate cancer therapy on efficacy and safety of relugolix versus leuprolide in men with advanced prostate cancer: Subgroup analysis from the phase III HERO study. J Clin Oncol.2021;39(6, suppl):28. Abstract 106. doi: 10.1200/JCO.2021.39.6_suppl.106
Shore ND, Saad F, Cookson MS, et al; HERO study investigators. Oral relugolix for androgen- deprivation therapy in advanced prostate cancer. N Engl J Med. 2020;382(23):2187-2196. doi: 10.1056/NEJMoa2004325
US Food & Drug Administration (FDA). FDA approves relugolix for advanced prostate cancer. December 18, 2020. https://www.fda.gov/drugs/drug-approvals-and-databases/fda- approves-relugolix-advanced-prostate-cancer