Relugolix superior to leuprolide acetate for advanced prostate cancer
Click Here to Manage Email Alerts
Relugolix demonstrated superiority over leuprolide acetate in sustained testosterone suppression through 48 weeks among men with advanced prostate cancer, according to study results presented during the ASCO20 Virtual Scientific Program.
Relugolix also achieved castration by day 4, resulted in faster testosterone recovery after discontinuation and reduced major adverse cardiovascular events by 50%, researchers who conducted the randomized phase 3 study noted.
“Cardiovascular mortality is the leading cause of death for patients with prostate cancer,” Neal D. Shore, MD, FACS, medical director of Carolina Urologic Research Center, said during the presentation. “Percentage of patients with prostate cancer dying of cardiovascular disease has surpassed the percentage of patient dying from prostate cancer itself since the 1990s.”
“About 30% of men with prostate cancer have known cardiovascular disease,” he added. “Many more of these patients have co-morbid risk factors such as obesity, diabetes and hypertension.”
Luteinizing hormone-releasing hormone agonists, such as leuprolide acetate, generally are used for medical castration in advanced prostate cancer. However, these drugs can lead to an initial testosterone surge with a delayed onset of castration and require a depot injection, according to study background.
Previous studies showed relugolix (Relumina, Myovant Sciences), the first oral gonadotropin-releasing hormone receptor antagonist, rapidly suppresses testosterone levels.
In the HERO III trial, Shore and colleagues compared the efficacy and safety of relugolix vs. leuprolide acetate among 934 men with androgen-sensitive advanced prostate cancer. The researchers randomly assigned the men 2:1 to relugolix dosed at 120 mg daily (n = 622) or to leuprolide acetate via 3-month depot injection (n = 308).
Achieving and maintaining serum testosterone suppression to castrate levels less than 50 ng/dL through 48 weeks served as the study’s primary endpoint.
Castration rates at day 4, rates of profound castration — defined as less than 20 ng/dL — at days 4 and 15, PSA response rate at day 15 and follicle-stimulating hormone (FSH) levels at week 25 served as secondary endpoints.
Researchers also evaluated testosterone recovery in a subset of 184 patients.
Results showed 96.7% (95% CI, 94.9-97.9) of men assigned relugolix achieved and maintained castration through 48 weeks compared with 88.8% of men on leuprolide acetate, demonstrating noninferiority with difference of 7.9% (95% CI, 4.1-11.8).
Testosterone suppression to less than 50 ng/dL at day 4 occurred among 56% of men in the relugolix group compared with no men in the leuprolide acetate group (P < 0.0001). At day 15, testosterone suppression to less than 50 ng/dL occurred among 98.71% of men in the relugolix group and 12.05% of men in the leuprolide group, with 78.38% of men on relugolix and 0.98% of men on leuprolide acetate achieving profound castration (P < 0.0001 for both).
Confirmed PSA response at day 15 followed by confirmation at day 29 occurred among 79.4% of men in the relugolix group and 19.8% of men in the leuprolide group (P < 0.0001). Mean FSH levels at day 1 of week 25 were 1.72 for the relugolix group and 5.95 for the leuprolide group.
Median testosterone levels among men in the testosterone recovery subset were 270.76 ng/dL in the relugolix group and 12.26 ng/dL in the leuprolide group 90 days after therapy discontinuation.
Incidence of major adverse cardiovascular events was lower in the relugolix group compared with the leuprolide group (2.9% vs. 6.2%).
“Risk of major adverse cardiovascular events was 54% lower in the Relugolix group compared with leuprolide, which is very encouraging,” Shore said. “Relugolix has the potential to become the new standard for androgen deprivation therapy in advanced prostate cancer.”
Collapse
Shore ND, et al. Abstract 5602. Presented at: ASCO20 Virtual Scientific Program; May 29-31, 2020.
Click Here to Manage Email Alerts