Phase 3 HERO Study Update Demonstrates Promise for Relugolix in Advanced Prostate Cancer

Daniel George, MD

Relugolix demonstrated a similar rate of castration resistance-free survival compared with the current standard of care leuprolide acetate as treatment of patients with metastatic prostate cancer, according to results from an additional secondary end point in the phase 3 HERO study.¹

The castration resistance-free survival rate, was 74% with relugolix versus 75% with leuprolide acetate, which did not achieve statistical superiority (HR, 1.03; 95% CI, 0.68-1.57; P =.84). The agent was previously granted a Priority Review designation from the FDA with a target action date of December 20, 2020. The results from the HERO study provide support for this designation, demonstrating a 97% response rate.

“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,” said Daniel George, MD, a professor of medicine and surgery at the Duke University School of Medicine and HERO program steering committee member, in a statement. “I continue to be excited by relugolix as a potential new and differentiated treatment option for men with prostate cancer given its robust clinical and safety data, including the lower risk of major adverse cardiovascular events compared to leuprolide acetate.”

The HERO study has demonstrated the superiority of relugolix over leuprolide in men with advanced prostate cancer, according to the findings presented during the 2020 American Society of Clinical Oncology Virtual Scientific Meeting.²

HERO is a randomized, open-label, parallel-group multinational clinical study evaluating the safety and efficacy of this agent in 934 men with androgen-sensitive prostate cancer. Patients had to have received at least 1 year of continuous androgen deprivation therapy (ADT) to be included in the study. Patients were randomized 2:1 to receive either a single loading dose of relugolix at 360 mg followed by a 120 mg dose daily or leuprolide acetate in a 3-month depot injection.

The primary end point of the study was sustained castration rate defined as the cumulative probability of testosterone suppression to ≤50 ng/dL. Secondary end points in this study included castration rate by visit, profound castration rate, prostate-specific antigen (PSA), PSA response rate, time to PSA progression, and quality of life (QoL). The HERO study also evaluated the QoL total scores and each subdomain score, castration resistance-free survival, composite of safety, the pharmacokinetics of relugolix, testosterone recovery, and sustained profound castration rate.

To be included in the study, patients had to have a histologically or cytologically confirmed diagnoses of adenocarcinoma of the prostate and were good candidates for 1 year on continuous ADT. Patients were also required to have an ECOG performance status of 0 or 1 at the time of both initial screening and baseline, a serum testosterone level of ≥150 ng/dL and a serum PSA concentration of >2.0 ng/mL (2.0 μg/L). Patients were excluded from the study if they required chemotherapy or surgery, had brain metastases, or had a history of surgical castration. Patients who had been treated with GnRH analog, another form of ADT, or had prior systemic cytotoxic treatment for prostate cancer were also excluded from the study.

The response rate was 96.7% in patients with castrate levels ≤50 ng/dL that were sustained from week 5 to 48 (95% CI, 94.9-97.9). The response rate was 88.8% in those treated with leuprolide, demonstrating a 7.9% difference between the 2 groups (95% CI, 4.1%-11.8%; P <.0001). The study achieved castration in patients with relugolix as early as day 4.

Superiority was demonstrated across all secondary end points with relugolix compared with leuprolide in the HERO study. The median T-levels among patients evaluated for testosterone recovery were 270.76 ng/dL in the relugolix group compared with 12.26 ng/dL in the control group 90 days after discontinuation of therapy.

Incidence of major adverse cardiovascular events was 2.9% with relugolix versus 6.2% with leuprolide in a prespecified analysis. The safety of these 2 agents also appeared to be similar. Adverse events (AEs) that occurred in at least 10% of the relugolix versus leuprolide groups, respectively, included hot flush (54.3% vs 51.6%), fatigue (21.5% vs 18.5%), 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%). Diarrhea was only observed in grades ½ with relugolix and did not result in treatment discontinuation.

The incidence of AEs in men with metastatic prostate cancer remained consistent with the previously observed findings from HERO, with no new safety signals observed.1

_References

_{1. Myovant sciences announces results of additional secondary endpoint of castration resistance-free survival from phase 3 hero study of relugolix in advanced prostate cancer. News Release. September 29, 2020. Accessed September 29, 2020. https://bit.ly/3kZ66i1}

_{2. Shore ND, George DJ, Saad F, et al. HERO phase III trial: Results comparing relugolix, an oral GnRH receptor antagonist versus leuprolide acetate for advanced prostate cancer. Presented at: 2020 ASCO Virtual Scientific Program. Abstract 5602.}