Relugolix: a novel androgen deprivation therapy for management of patients with advanced prostate cancer

Abstract

Androgen deprivation therapy (ADT) is the foundation of treatment for patients with locally advanced, recurrent and metastatic prostate cancer, most commonly using luteinizing releasing hormone (LHRH) agonists. More recently, a new approach to ADT has emerged with the development of gonadotropin-releasing hormone (GnRH) antagonists, which aim to overcome some of the potential adverse physiologic effects of LHRH agonists. This article focuses on the newest GnRH antagonist, relugolix – a once-daily treatment and the only oral GnRH antagonist that has now been approved for the treatment of advanced prostate cancer. In phase II and III studies, relugolix achieved rapid and sustained castration without the testosterone surge associated with LHRH agonists, thus avoiding the potential clinical consequences of tumor flare and the necessity for concomitant anti-androgen therapy. Relugolix also achieved rapid testosterone recovery, which may potentially reduce ADT-related adverse events and offer opportunities for combination and intermittent therapy strategies. Cardiovascular safety is a particular concern in men with prostate cancer and ADT further increases cardiovascular risk: indeed, LHRH agonists are required to have a drug label warning about an increased risk of cardiovascular disease. Data from the phase III HERO study demonstrate an improved cardiac safety profile for the GnRH antagonist relugolix compared with the LHRH agonist leuprolide, including a significantly reduced risk for a major adverse cardiovascular event. Taken together, the data indicate that relugolix may mitigate some of the cardiovascular concerns surrounding ADT and has the potential to become a new standard of care for men with prostate cancer. In summary, relugolix represents a novel and recently available prostate cancer management strategy, incorporating the mechanistic advantages of GnRH antagonists and the potential benefits of oral administration.

Relugolix: A Review in Advanced Prostate Cancer

“…Another area of interest for future study is on intermittent versus continuous relugolix treatment. Indeed, in the context of intermittent ADT for prostate cancer, the once-daily dosing, the rapid onset of action, and the apparent more rapid testosterone recovery associated with relugolix could potentially help facilitate more precise or targeted ADT [ 27 ]. The testosterone recovery observed with relugolix may have other clinically meaningful benefits, for example for men receiving a short course of ADT, or for men unable to tolerate adverse effects of testosterone suppression [ 12 ].…”

A case of lichenoid drug eruption associated with relugolix

“… 1 , 2 Relugolix, compared to leuprolide, has shorter time to testosterone suppression, higher rate of sustained testosterone suppression, and faster testosterone recovery upon therapy completion. 3 , 4 We describe, to our knowledge, the first case of a moderate skin rash in a male patient undergoing relugolix treatment for metastatic prostate cancer.…”

Review of Cardiovascular Risk of Androgen Deprivation Therapy and the Influence of Race in Men with Prostate Cancer

“…As detailed earlier in this paper, many researchers have found that GnRH antagonists like degarelix have fewer associated CV adverse events than their agonist counterparts [ 24 , 26 , 29 , 31 ]. Relugolix may be given additional consideration due to recent clinical trial data showing very low associated CV risk [ 68 , 69 ]. Androgen synthesis inhibitors (i.e., abiraterone) and androgen receptor antagonists (i.e., enzalutamide) have become key agents for castration sensitive and resistant PCa; however, they also can carry increased CV risk, and clinicians should take appropriate measures to monitor and modify their CV risk factors.…”