Relugolix: A Review in Advanced Prostate Cancer

Relugolix (Orgovyx((R))), an orally active nonpeptide gonadotropin-releasing hormone (GnRH) receptor antagonist that provides rapid testosterone suppression, is indicated in the USA for the treatment of advanced prostate cancer and in the EU for advanced hormone-sensitive prostate cancer. In the pivotal phase III HERO trial in men with advanced prostate cancer, once-daily oral relugolix (with a loading dose on day 1) led to a sustained castration rate over 48 weeks of treatment of > 90%, a rate that was non-inferior to that provided by intramuscular leuprolide depot every 3 months (with an exploratory analysis further indicating the superiority of relugolix over leuprolide). Relugolix was generally well tolerated, having an adverse event profile that is consistent with testosterone suppression. Furthermore, there is evidence that relugolix may be associated with a lower risk of major adverse cardiac events compared with leuprolide. With the ability to provide the rapid testosterone suppression (with no initial surge in testosterone upon treatment initiation) combined with the benefits of oral administration and potentially improved cardiac safety, relugolix presents a valuable treatment option for men with advanced prostate cancer where androgen deprivation therapy is indicated. Plain Language Summary Androgen deprivation therapy (ADT), a key component of prostate cancer treatment, reduces testosterone production to slow disease progression. Relugolix (Orgovyx((R))), from a class of drugs known as gonadotropin-releasing hormone (GnRH) receptor antagonists, is approved for the treatment of advanced prostate cancer. Whereas some ADT agents (i.e. GnRH agonists) produce an initial surge in testosterone levels (with the potential to cause a flare in disease symptoms), GnRH receptor antagonists, of which relugolix is the first available as an oral medication, provide rapid testosterone suppression with no initial surge. In a key clinical trial in men with advanced prostate cancer, once-daily relugolix provided sustained castration in > 90% of patients, with a sustained castration rate that was non-inferior to that of a comparator agent (leuprolide) administered by intramuscular injection every 3 months. Relugolix was generally well tolerated and may be associated with a lower risk of major adverse cardiac events than leuprolide. Providing rapid and sustained testosterone suppression, combined with the benefits of oral administration and potentially improved cardiac safety, relugolix presents a valuable treatment option for ADT in men with advanced prostate cancer.