MP24-07 RELUGOLIX VS LEUPROLIDE EFFECTS ON CASTRATION RESISTANCE-FREE SURVIVAL FROM THE PHASE 3 HERO STUDY IN MEN WITH ADVANCED PROSTATE CANCER

Abstract

INTRODUCTION AND OBJECTIVE: Androgen deprivation therapy is a foundational therapy for achieving castration levels for men with advanced prostate cancer (aPC). Relugolix, an FDA‐approved, oral GnRH receptor antagonist, demonstrated suppression of testosterone to castrate levels in 96.7% of men, which was superior to leuprolide (88.8%), and a 54% risk reduction in major adverse cardiovascular events relative to leuprolide in the phase 3 HERO study (NCT03085095). METHODS: The HERO study was a multinational phase 3 randomized, open‐label, parallel group study to evaluate the safety and efficacy of relugolix in men with aPC. Men were randomized 2:1 to receive relugolix 120 mg orally once‐daily after a single loading dose of 360 mg or leuprolide 3‐monthly injections for 48 weeks. To further characterize the efficacy profile of relugolix, the HERO study randomized an additional 101 men to assess a secondary end point of castration resistance‐free survival (CRFS) during 48‐weeks of treatment in men with metastatic prostate cancer, a clinically relevant indicator of disease progression in the final analysis. CRFS was defined as the time from the date of first dose to the date of confirmed prostate‐specific antigen progression (defined by Prostate Cancer Clinical Trials Working Group 3) while castrated or death due to any reason, whichever occurs earlier. The CRFS analysis was conducted in the metastatic disease cohort as well as the overall modified intention‐to‐treat (mITT) population. RESULTS: Overall, 1074 men with aPC (relugolix: n=717; leuprolide: n=357) and 434 men with metastatic disease (relugolix: n =290; leuprolide: n=144) were included in the CRFS analysis (mITT population). Mean age of men with metastatic disease was 71 years, with 29% of men over 75 years of age. Men included in the analysis were from North and South America (28.9% and 6.4%), Europe (37.8%), and Asia/rest of world (26.9%). At study entry, the most common location of metastasis was bone only (53%). CRFS rates at week 48 in the metastatic disease cohort were 74.3% (95% CI: 68.6%, 79.2%) and 75.3% (95% CI: 66.7%, 81.9%) in the relugolix and leuprolide groups, respectively (hazard ratio: 1.03 =0.68, 1.57]; p=0.84). Results were similar in the overall mITT population. No new safety findings were identified. CONCLUSIONS: In the HERO study, CRFS assessed during the 48‐week treatment of relugolix was not significantly different than standard‐of‐care leuprolide in the subgroup of men with metastatic disease or in the overall mITT population.