Relugolix is the first oral gonadotrophin-releasing hormone (GnRH) receptor antagonist. Based on the phase III HERO trial results, relugolix received Food and Drug Administration approval for adult patients with advanced prostate cancer (PCa).
: We provide an overview of the preclinical and clinical development of relugolix and its role in the current treatment landscape of PCa.
Relugolix leads to rapid inhibition of testicular production of testosterone and its rapid recovery upon discontinuation. In the HERO trial, relugolix was associated with a superior cardiovascular safety profile compared to GnRH agonists. These attributes make relugolix a promising therapy for patients with pre-existing cardiovascular co-morbidities, those pursuing intermittent androgen deprivation therapy, and those who desire rapid testosterone recovery during "off-treatment" periods. In the HERO trial, very few patients received concomitant enzalutamide (n=17, 2.7%) or docetaxel (n<10, 1.3%). Safety of relugolix has not been established in combination with many androgen-receptor-axis targeted therapies (e.g. abiraterone, apalutamide), cabazitaxel, or lutetium Lu 177 vipivotide tetraxetan, which precludes its use in combination with these agents. In addition, being an oral drug, relugolix may also be associated with challenges of affordability, adherence, and compliance in this predominantly elderly population.
Expert review of anticancer therapy. 2022 Jul 22 [Epub ahead of print]
Kamal Kant Sahu, Nishita Tripathi, Neeraj Agarwal, Umang Swami
Division of Hematology and Medical Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah 84112, United States.