Oral Relugolix for Androgen-Deprivation Therapy in Advanced Prostate Cancer
Comments: The HERO trial is an international, multicenter study comparing Relugolix (an oral androgen deprivation therapy agent given 120 mg orally, once daily) to leuprolide (22.5 mg injection, every 3 months) for 48 weeks.
The primary end point of the study was the sustained suppression of testosterone to castrate levels, defined as testosterone less than 50 ng/dL for up to 48 weeks. Secondary end points included early suppression of testosterone at days 4, 15, and 28, and the rate of achieving very low testosterone levels of less than 20 ng/dL while on treatment.
In this trial involving men with advanced prostate cancer, relugolix achieved rapid, sustained suppression of testosterone levels that was superior to that with leuprolide, with a 54% lower risk of major adverse cardiovascular events.
The FDA is expected to make a decision on approval of this for this indication by 20th Dec. 2020. It is best to await for this approval.
Dr Rajeentheran Suntheralingam
Consultant Urologist / Urological Surgeon
See the following link to that abstract:
https://www.nejm.org/doi/full/10.1056/NEJMoa2004325
Oral Relugolix for Androgen-Deprivation Therapy in Advanced Prostate Cancer
List of authors.
Abstract
Background
Injectable luteinizing hormone–releasing hormone agonists (e.g., leuprolide) are the standard agents for achieving androgen deprivation for prostate cancer despite the initial testosterone surge and delay in therapeutic effect. The efficacy and safety of relugolix, an oral gonadotropin-releasing hormone antagonist, as compared with those of leuprolide are not known.
Methods
In this phase 3 trial, we randomly assigned patients with advanced prostate cancer, in a 2:1 ratio, to receive relugolix (120 mg orally once daily) or leuprolide (injections every 3 months) for 48 weeks. The primary end point was sustained testosterone suppression to castrate levels (<50 ng per deciliter) through 48 weeks. Secondary end points included noninferiority with respect to the primary end point, castrate levels of testosterone on day 4, and profound castrate levels (<20 ng per deciliter) on day 15. Testosterone recovery was evaluated in a subgroup of patients.
Results
A total of 622 patients received relugolix and 308 received leuprolide. Of men who received relugolix, 96.7% (95% confidence interval [CI], 94.9 to 97.9) maintained castration through 48 weeks, as compared with 88.8% (95% CI, 84.6 to 91.8) of men receiving leuprolide. The difference of 7.9 percentage points (95% CI, 4.1 to 11.8) showed noninferiority and superiority of relugolix (P<0.001 for superiority). All other key secondary end points showed superiority of relugolix over leuprolide (P<0.001). The percentage of patients with castrate levels of testosterone on day 4 was 56.0% with relugolix and 0% with leuprolide. In the subgroup of 184 patients followed for testosterone recovery, the mean testosterone levels 90 days after treatment discontinuation were 288.4 ng per deciliter in the relugolix group and 58.6 ng per deciliter in the leuprolide group. Among all the patients, the incidence of major adverse cardiovascular events was 2.9% in the relugolix group and 6.2% in the leuprolide group (hazard ratio, 0.46; 95% CI, 0.24 to 0.88).
Conclusions
In this trial involving men with advanced prostate cancer, relugolix achieved rapid, sustained suppression of testosterone levels that was superior to that with leuprolide, with a 54% lower risk of major adverse cardiovascular events. (Funded by Myovant Sciences; HERO ClinicalTrials.gov number, NCT03085095. opens in new tab.)
