Relugolix, A Novel Oral GnRH Receptor Antagonist, versus Leuprolide Depot for Prostate Cancer: The HERO Phase 3 Trial

5602 Background: LHRH agonists are the mainstay for medical castration in advanced prostate cancer; however, they cause an initial testosterone (T) surge with a delayed onset of castration and require depot injection. Relugolix is the first oral GnRH receptor antagonist, which was previously shown to rapidly suppress T levels. The HERO trial compared the safety and efficacy of relugolix with leuprolide acetate in advanced prostate cancer patients. Methods: HERO is a 48-week, global, pivotal phase III trial that randomized 934 patients with androgen-sensitive advanced prostate cancer in a 2:1 ratio to receive relugolix 120 mg orally QD after a single l or leuprolide acetate 3-month depot injection. The primary endpoint was to achieve and maintain serum T suppression to castrate levels (< 50 ng/dL) through 48 weeks. Key secondary endpoints included castration rates at Day 4, profound castration (< 20 ng/dL) rates at Days 4 and 15, PSA response rate at Day 15 and FSH levels at Week 25. Testosterone recovery was evaluated in a subset of 184 patients. Results: A total of 96.7% (95% CI: 94.9%, 97.9%) of men on relugolix achieved and maintained castration through 48 weeks compared to 88.8% on leuprolide. The difference of 7.9% (95% CI: 4.1%, 11.8%) demonstrated non-inferiority (margin -10%) and superiority (P < 0.0001) of relugolix to leuprolide. All key secondary efficacy endpoints tested demonstrated superiority over leuprolide (P < 0.0001) (Table). In the testosterone recovery subset, median T levels were 270.76 ng/dL in the relugolix compared to 12.26 ng/dL in the leuprolide group 90 days after discontinuation of therapy. In a prespecified analysis, the incidence of major adverse cardiovascular events (MACE) was lower in the relugolix group than in the leuprolide group (2.9% vs. 6.2%, respectively); otherwise the safety and tolerability profiles were generally similar. Conclusion: Relugolix achieved castration as early as Day 4 and demonstrated superiority over leuprolide in sustained T suppression through 48 weeks, faster T recovery after discontinuation and a 50% reduction in MACE. Relugolix has the potential to become a new standard for T suppression for patients with advanced prostate cancer. Clinical trial information: NCT03085095 . [Table: see text]

Download Full-text

The efficacy and safety of degarelix, a GnRH receptor antagonist: A multicenter, randomized, maintenance dose-finding phase II study with Japanese prostate cancer patients.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.7_suppl.154 ◽

2011 ◽

Vol 29 (7_suppl) ◽

pp. 154-154

Author(s):

S. Ozono ◽

T. Ueda ◽

S. Hoshi ◽

A. Yamaguchi ◽

H. Maeda ◽

...

Keyword(s):

Prostate Cancer ◽

Adverse Events ◽

Receptor Antagonist ◽

Phase Ii ◽

Initial Dose ◽

Maintenance Dose ◽

Gnrh Receptor ◽

Dose Finding ◽

Phase Iii ◽

Efficacy And Safety

154 Background: Degarelix, a GnRH receptor antagonist inducing rapid, profound and sustained suppression of serum testosterone levels, without testosterone surge, was evaluated in a phase II dose finding study in Japan. Methods: A total of 278 patients with adenocarcinoma of the prostate were randomized and 273 patients (any stage; median age, approx. 76 years; median testosterone, 4.46 ng/mL; median prostate-specific antigen (PSA) level, 22.8 ng/mL) received study treatment. Degarelix was administered subcutaneously at an initial dose of 240 mg followed by monthly maintenance doses of either 80 mg or 160 mg. The treatment continued for 12 months in the study. Results: The primary endpoint was the proportion of patients with testosterone suppression to castrate level of ≤0.5 ng/mL during 12 months treatment. Both dose regimens of 80 mg and 160 mg kept 94.5% and 95.2% of patients on castrate level respectively throughout the treatment period. At 3 days of treatment, approximately 99% of the patients reached the castrate level without testosterone surge. The percentage change in serum PSA reduction exceeded 76% at 4 weeks. The overall tumor response rates (proportion of patients with complete and partial responses) were from 77.4% to 90.8% across the groups. Eighteen patients (6.6%) withdrew from the study due to adverse events. The most common adverse events were injection site reactions; other adverse events included pyrexia, weight increased, hypertension and hot flush. Degarelix appeared well tolerated. Conclusions: With an initial dose of 240 mg followed by monthly maintenance doses of 80 mg or 160 mg, Degarelix resulted in a rapid profound and sustained testosterone suppression to castrate level and PSA reduction without testosterone surge for 12 months. Degarelix was well tolerated. The maintenance doses of 80 mg and 160 mg had similar efficacy and safety profiles. The study shows results similar to those from the degarelix pivotal phase III study (CS21). Assessment of risk-benefit would support the recommendation of the maintenance dose of 80 mg as a safe and effective monthly dose for the treatment of prostate cancer. [Table: see text]

Download Full-text

Relugolix is the first and currently only Orally-Administered GnRH Receptor Antagonist Approved for the treatment of Prostate Cancer: A Review

Asian Journal of Pharmaceutical Research ◽

10.52711/2231-5691.2021.00043 ◽

2021 ◽

pp. 247-250

Author(s):

Sunil R Bavaskar ◽

Mayur R. Bhurat

Keyword(s):

Prostate Cancer ◽

Receptor Antagonist ◽

Therapeutic Option ◽

Uterine Fibroids ◽

Subcutaneous Administration ◽

Symptomatic Treatment ◽

The United States ◽

Gnrh Receptor ◽

Ease Of Use ◽

Brand Name

Relugolix is a gonadotropin-releasing hormone (GnRH) receptor antagonist used in the treatment of several hormone-responsive conditions. It was first approved in Japan in 2019, under the brand name Relumina, for the symptomatic treatment of uterine fibroids, and more recently by the United States' FDA in 2020, under the brand name Orgovyx, for the treatment of advanced prostate cancer. Relugolix has also been studied in the symptomatic treatment of endometriosis. Relugolix is the first (and currently only) orally-administered GnRH receptor antagonist approved for the treatment of prostate cancer-similar therapies such as degarelix require subcutaneous administration-and therefore provides a less burdensome therapeutic option for patients who might otherwise require clinic visits for administration by healthcare professionals.In addition to its relative ease-of-use, relugolix was shown to be superior in the depression of testosterone levels when compared to leuprolide, another androgen deprivation therapy used in the treatment of prostate cancer1,2

Download Full-text