Prostate cancer: Oral relugolix bests inj leuprolide for rapid testosterone suppression
USA: The use of oral relugolix in men with prostate cancer may help to achieve rapid, sustained suppression of testosterone levels as compared to leuprolide, according to a recent study. The study published in the New England Journal of Medicine, also found oral relugolix to be associated with a 54% lower risk of major adverse cardiovascular events.
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. Relugolix is a novel, oral GnRH receptor antagonist that achieves both LH and FSH suppression to its direct inhibitory effect on the pituitary GnRH receptors. This direct inhibition does not result in a testosterone surge. There no information on the efficacy and safety of relugolix as compared to leuprolide.
For the purpose, Neal D. Shore, medical director for the Carolina Urologic Research Center, and colleagues 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. A total of 622 patients received relugolix and 308 received leuprolide.
The primary endpoint was sustained testosterone suppression to castrate levels (<50 ng per deciliter) through 48 weeks. Secondary endpoints included noninferiority with respect to the primary endpoint, 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.
Key findings of the study include:
- Of men who received relugolix, 96.7% maintained castration through 48 weeks, as compared with 88.8% of men receiving leuprolide.
- The difference of 7.9 percentage points showed noninferiority and superiority of relugolix.
- All other key secondary end points showed superiority of relugolix over leuprolide.
- 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).
"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," concluded the authors.
The study, "Oral Relugolix for Androgen-Deprivation Therapy in Advanced Prostate Cancer," is published in the New England Journal of Medicine.