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Relugolix was not found to achieve statistical superiority with regard to castration resistance–free survival versus leuprolide acetate in patients with metastatic prostate cancer through 48 weeks.
Relugolix was not found to achieve statistical superiority with regard to castration resistance–free survival versus leuprolide acetate (Lupron) in patients with metastatic prostate cancer through 48 weeks, according to updated data from the phase 3 HERO trial (NCT03085095).1
Results showed that 74% of men with metastatic disease who received relugolix were castration resistance–free through 48 weeks versus 75% of those who received leuprolide acetate (HR, 1.03; 95% CI, 0.68-1.57; P =.84).
For the secondary end point analysis, investigators defined castration resistance–free survival as the time from the first dose of treatment to prostate-specific antigen (PSA) progression via the Prostate Cancer Clinical Trials Working Group 3 criteria or death of any cause. Moreover, PSA progression was defined as increased PSA of 25% or more and 2 ng/mL or higher above the nadir; this had to be confirmed via a second PSA value 3 or more weeks later.
“These new data from the phase 3 HERO study show that 3 out of 4 men with metastatic prostate cancer remained castration resistance–free through 48 weeks while on oral relugolix, in-line with leuprolide acetate injections, the current standard of care,” Dan George, MD, a professor of medicine and surgery at the Duke University School of Medicine and HERO program steering committee member, stated in a press release.
“I continue to be excited by relugolix as a potential new and differentiated treatment option for men with prostate cancer given the robust clinical and safety data, including the lower risk of major adverse cardiovascular events (MACE) compared to leuprolide acetate,” George added.
In June 2020, the oral gonadotropin-releasing hormone receptor antagonist was granted a priority review designation from the FDA for use as a treatment in patients with advanced prostate cancer based on earlier data from HERO, which showed that relugolix was superior to leuprolide acetate with regard to providing sustained T-cell suppression through 48 weeks, rapid T-recovery following discontinuation, and a 50% reduction in MACE in this patient population.2,3
In the international phase 3 trial, a total of 934 patients with androgen-sensitive advanced prostate cancer were randomized in a 2:1 fashion to receive either oral relugolix at a daily dose of 120 mg after 1 one-time loading dose of 360 mg (n = 624) or a 3-month depot injection of leuprolide acetate (n = 310). In a subset of 184 patients, investigators also assessed testosterone recovery.
The primary end point of the trial was to both achieve and maintain serum T-suppression to castrate levels, defined as lower than 50 ng/dL, through 48 weeks. Key secondary end points of the trial were comprised of castration rates at day 4 and day 15, profound castration rates of less than 20 ng/dL at days 4 and 15, PSA response rate at day 15, and follicle-stimulating hormone levels at week 24.
To participate, patients had to have confirmed advanced disease, have received at least 1 year of androgen deprivation therapy (ADT), have a serum PSA that was higher than 2.0 ng/mL, and an ECOG performance status of 0-1. If patients were anticipated to undergo chemotherapy or surgery within 2 months of receiving ADT, had prior ADT for more than 18 months for prior systemic cytotoxic treatment for their disease, had active liver disease, or severe cardiovascular risk conditions, they were excluded from enrollment on the trial.
In the trial, 90.2% (n = 563) of patients who received relugolix completed treatment versus 89.0% (n = 276) of those who received standard of care. Additionally, 9.5% versus 10.3% of patients on the relugolix and leuprolide arms, respectively, discontinued treatment early. The remaining patients underwent randomization but did not receive treatment.
Baseline patient characteristics were reportedly well balanced between the 2 treatment arms. Notably, 50.2% of patients who enrolled on the trial had biochemical recurrence following definitive treatment for their disease, 28.9% were enrolled in North America, while 11.5% were enrolled in Japan. Over 90% of participants had at least 1 cardiovascular risk factor.
Additional results showed that in a subgroup of patients who were tested for testosterone recovery, the median T-levels 90 days after treatment discontinuation were 270.76 ng/dL and 12.26 ng/dL in the relugolix and leuprolide arms, respectively.
With regard to safety, the incidence of MACE was lower in the investigational arm compared with the control arm, at 2.9% versus 6.2%, respectively. The safety and tolerability of the 2 drugs were comparable beyond that factor. The toxicities that occurred in more than 10% of patients treated with either agent included hot flash (54.3% with relugolix vs 51.6% with leuprolide), fatigue (21.5% vs 18.5%, respectively), constipation (12.2% vs 9.7%), diarrhea (12.2% vs 6.8%), arthralgia (12.1% vs 9.1%), and hypertension (7.9% vs 11.7%).
“We believe the totality of data – including previously reported data from the phase 3 HERO program, published in the New England Journal of Medicine – presents compelling evidence for the potential use of relugolix in men with advanced prostate cancer,” Lynn Seely, MD, chief executive officer of Myovant Sciences, added in the release. “With our new drug application under priority review by the FDA, we look forward to our target action date in December 2020 and hope to advance our commitment to redefining care by bringing once-daily, oral relugolix to men with prostate cancer.”