Relugolix Rapidly Suppresses Testosterone Levels in Advanced Prostate Cancer

In a phase 3 study of patients with advanced prostate cancer, relugolix yielded rapid, sustained testosterone level suppression and a lower risk for major cardiovascular adverse events than leuprolide (N Engl J Med. 2020 May 29. Epub ahead of print).

“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,” wrote Neal D. Shore, MD, Carolina Urologic Research Center, Myrtle Beach, South Carolina, and co-investigators.

Based on a lack of information regarding how the safety and efficacy of relugolix compares with that of leuprolide, Dr Shore et al conducted a study of 930 patients with advanced prostate cancer. These patients were randomized in a 2:1 ratio to receive relugolix 120 mg once daily (n = 622) or leuprolide every 3 months (n = 308) for 48 weeks.

Sustained testosterone suppression to castrate levels (<50 ng per deciliter) through week 48 was the main end point of the study. Noninferiority with respect to the main end point, castrate levels of testosterone on day 4, and profound castrate levels (<20 ng per deciliter) on day 1 were the secondary end points.

In addition, the investigators assessed testosterone recovery in a patient subgroup.

Among the recipients of relugolix, 96.7% (95% CI, 94.9-97.9) maintained castration through 48 weeks versus 88.8% (95% CI, 84.6-91.8) of leuprolide recipients. According to Dr Shore and colleagues, the 7.9 percentage point difference (95% CI, 4.1 to 11.8) demonstrated the noninferiority and superiority of relugolix (P <.001 for superiority). In addition, every other key secondary end point showed the superiority of relugolix over leuprolide (P <.001).

In the relugolix and leuprolide arms, patients had castrate levels of testosterone on day 4 that were 56.0% and 0%, respectively, and the incidence of major cardiovascular adverse events was 2.9% and 6.2% with relugolix and leuprolide, respectively (hazard ratio, 0.46; 95% CI, 0.24-0.88).

In a subgroup comprising 184 patients who were followed for testosterone recovery, the mean testosterone levels 90 days post-treatment were 288.4 ng per deciliter and 58.6 ng per deciliter in the relugolix and leuprolide arms, respectively.

“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,” Dr Shore and co-investigators concluded.—Hina Porcelli