Treatment with relugolix achieved a high rate of sustained testosterone suppression to castrate levels in patients with androgen-sensitive advanced prostate cancer, meeting the primary endpoint of the phase III HERO trial.
Neal Shore, MD
Treatment with relugolix achieved a high rate of sustained testosterone suppression to castrate levels in patients with androgen-sensitive advanced prostate cancer, meeting the primary endpoint of the phase III HERO trial (NCT03085095).1
Specifically, results showed that in the primary endpoint responder analysis, 96.7% (95% CI, 94.9%-97.9%) of men receiving once-daily, oral relugolix achieved sustained testosterone suppression to castrate levels (≤50 ng/dL) from weeks 5 through 48. The endpoint was met if the lower bound of the 95% confidence interval of the response rate was ≥90%.
The data will serve as support for a new drug application (NDA) to the FDA, which is anticipated to be submitted in the second quarter for 2020, Myovant Sciences, the developer of the oral gonadotropin-releasing hormone (GnRH) receptor antagonist, stated in a press release. The company added that the findings will also be included in future regulatory submissions in Europe and Japan.
“An oral gonadotropin-releasing hormone, or GnRH, antagonist for advanced prostate cancer has been an aspiration for many years,” Neal Shore, MD, medical director of the Carolina Urologic Research Center and HERO Program Steering Committee Member, stated in the press release. “If approved, relugolix would become the first-of-its-kind oral option for men with advanced prostate cancer.”
In the international, open-label, parallel-group, phase III HERO trial, patients with androgen-sensitive advanced prostate cancer who required ≥1 year of continuous androgen deprivation therapy (ADT) were randomized 2:1 to receive a single loading dose of relugolix at 360 mg followed by relugolix at 120 mg once daily, or leuprolide acetate 3-month depot injection.
The trial, which is still recruiting, is planning to enroll 1100 patients, including those with metastatic prostate cancer that will support an analysis of castration resistance—free survival (n = 430), and Chinese patients that will support registration in China (n = 138).
To be eligible for enrollment, patients must have histologically or cytologically confirmed prostate cancer and is a candidate for ≥1 year of ADT, has a serum testosterone of ≥150 ng/dL at time of screening, has a serum prostate-specific antigen (PSA) concentration of >2.0 ng/mL at screening, and an ECOG performance status of 0 or 1.
Patients who are likely to require chemotherapy or surgery within 2 months of initiating ADT, previously received an GnRH analog or another form of ADT for >18 months, received prior systemic treatment for prostate cancer, have brain metastases, are scheduled for major surgery after baseline, and have a history of surgical castration cannot enroll on the study.
The primary endpoint of the study, which will be used for FDA approval, is the ability of relugolix to achieve and maintain testosterone suppression to castrate levels through 48 weeks.
Relugolix also demonstrated superiority over leuprolide acetate in 6 of the study’s secondary endpoints, including rapid suppression of testosterone at day 4 and day 15, profound suppression of testosterone at day 15, rapid suppression of prostate-specific antigen (PSA) at day 15, and suppression of follicle-stimulating hormone at week 24 (all P values <.0001).
Relugolix also showed noninferiority to leuprolide acetate on sustained testosterone suppression through 48 weeks (96.7% vs 88.8%, respectively) with a between-group difference of 7.9% (95% CI, 4.1%-11.8%), which is the primary endpoint required for regulatory submissions outside of the United States.
Moreover, pharmacodynamic data showed that there was no testosterone flare after initiation of relugolix and mean testosterone levels returned to normal levels within 90 days after treatment discontinuation.
Regarding safety, the overall incidence of adverse events (AEs) in the relugolix and leuprolide acetate arms was comparable at 92.9% vs 93.5%, respectively. A total 3.5% of patients on relugolix discontinued the trial early due to AEs versus 2.6% of those on leuprolide acetate.
The most frequently reported AEs (≥10%) in the relugolix arm included hot flashes, fatigue, constipation, diarrhea, and arthralgia. Additionally, unadjudicated major adverse cardiovascular events—which included non-fatal myocardial infarction, non-fatal stroke, and all-cause mortality—were reported in 2.9% versus 6.2% of those on relugolix and leuprolide acetate, respectively.
Prior phase II results also demonstrated efficacy with relugolix in patients with metastatic or locally advanced prostate cancer who were deemed appropriate for ADT.2 In the study, patients were randomized to 2 different doses of relugolix and leuprorelin. Results showed that relugolix had a tolerable safety profile, and that after 24 weeks, PSA levels were reduced by 97.3% to a median of 0.1 ng/mL compared with 92.4% with a median 0.2 ng/mL with leuprorelin.
“With the exciting results from the HERO study demonstrating the potential of relugolix to provide unique benefits compared to leuprolide, we look forward to submitting an NDA to the FDA,” Lynn Seely, MD, president and CEO of  Myovant Sciences, stated in the press release. “We are now closer to our goal of bringing a precision oral medicine to the broad spectrum of men with advanced prostate cancer.”