Relugolix Wins Approval in Canada for Advanced Prostate Cancer

Health Canada has approved the oral gonadotropin-releasing hormone receptor antagonist relugolix (Orgovyx) for the treatment of men with advanced prostate cancer, according to an announcement from Sumitomo Pharma.¹

The regulatory decision was supported by data from the phase 3 HERO trial (NCT03085095). Findings showed that of patients treated with relugolix (n = 622), 96.7% (95% CI, 94.9%-97.9%) maintained castration through 48 weeks compared with 88.8% (95% CI, 84.6%-91.8%) of those treated with leuprolide (Lupron; n = 308). The difference of 7.9% (95% CI, 4.1%-11.8%) demonstrated noninferiority and superiority of relugolix (P < .001).²

“Roughly 1 in 8 Canadian men will develop prostate cancer in their lifetime, and the ability to suppress testosterone, primarily achieved through androgen deprivation therapy [ADT], is foundational in the treatment of the advanced stages of the disease,” Fred Saad, MD, FRCS, professor and chairman of the Department of Surgery and director of Genitourinary Oncology at the University of Montreal, in Quebec, Canada, stated in a news release.¹ “In the HERO study, [relugolix] demonstrated rapid, sustained, and profound testosterone suppression when compared with leuprolide. [Relugolix] is the first approved ADT in Canada that can be administered orally, and once daily, offering a safe and effective option for advanced prostate cancer patients in the country.”

In December 2020, the FDA approved relugolix as a treatment for patients with advanced prostate cancer, based on data from HERO.³

The international, randomized, open-label trial enrolled patients at least 18 years of age with histologically or cytologically confirmed adenocarcinoma of the prostate who were candidates for at least 1 year of continuous ADT.²

Patients needed to have 1 of 3 clinical disease presentations:

• Evidence of biochemical relapse via prostate-specific antigen or clinical relapse after local primary intervention with curative intent
• Newly diagnosed, metastatic hormone-sensitive prostate cancer
• Advanced localized disease unlikely to be cured through local primary intervention with curative intent

Patients who experienced major cardiovascular adverse effects (AEs) within 6 months before enrollment were not included.

Investigators randomly assigned patients 2:1 to receive either 120 mg of oral relugolix per day following an initial single loading dose of 360 mg, or 22.5 mg of leuprolide acetate injected once every 3 months for 48 weeks.

Patients were stratified by geographic region (North and South America vs Europe vs Asia–Pacific region), metastatic disease (present vs absent), and age (≤75 years vs >75 years).

Sustained testosterone suppression to castrate levels of less than 50 ng/dL through 48 weeks served as the trial’s primary end point. Secondary end points included noninferiority for relugolix with respect to the primary end point, castrate levels of testosterone on day 4, and profound castrate levels on day 15.

Relugolix demonstrated superiority vs leuprolide with respect to all key secondary end points.

Regarding safety, major cardiovascular AEs occurred in 2.9% of patients in the relugolix arm vs 6.2% of patients in the leuprolide group (HR, 0.46; 95% CI, 0.24-0.88).

Any-grade AEs occurred in 92.9% of patients in the experimental arm vs 93.5% of patients in the control arm. The rates of grade 3 or 4 AEs were 18.0% and 20.5%, respectively. Any-grade serious AEs were reported in 12.2% of patients in the relugolix group vs 15.3% of patients in the leuprolide group. The rates of grade 3 or 4 serious AEs were 9.8% and 11.4%, respectively.

AEs leading to death occurred in 1.1% of patients in the experimental arm vs 2.9% of patients in the control arm.

The most common any-grade AEs reported in at least 10% of patients included hot flash (54.3% and 51.6% with relugolix and leuprolide, respectively), fatigue (21.5% and 18.5%), constipation (12.2% and 9.7%), diarrhea (12.2% and 6.8%), arthralgia (12.1% and 9.1%), and hypertension (7.9% and 11.7%).

References

1. Sumitomo Pharma announces authorization in Canada of Orgovyx (relugolix) for the treatment of men with advanced prostate cancer. News release. Sumitomo Pharma. October 23, 2023. Accessed October 23, 2023. https://news.us.sumitomo-pharma.com/2023-10-23-Sumitomo-Pharma-Announces-Authorization-in-Canada-of-ORGOVYX-R-relugolix-for-the-Treatment-of-Men-with-Advanced-Prostate-Cancer
2. Shore ND, Saad F, Cookson MS, et al. Oral relugolix for androgen-deprivation therapy in advanced prostate cancer. N Engl J Med. 2020;382(23):2187-2196. doi:10.1056/NEJMoa2004325
3. FDA approves first oral hormone therapy for treating advanced prostate cancer. News release. FDA. December 18, 2020. Accessed October 23, 2023. https://www.fda.gov/news-events/press-announcements/fda-approves-first-oral-hormone-therapy-treating-advanced-prostate-cancer