Relugolix vs. Leuprolide Effects on Castration Resistance-Free Survival from the Phase 3 HERO Study in Men with Advanced Prostate Cancer

SIMPLE SUMMARY: An advanced prostate cancer research study known as HERO compared the ability of the medications relugolix and leuprolide to lower testosterone. The goal was to lower the testosterone to sustained castration levels, which is defined as below 50 ng/dL. This analysis evaluated how long an individual’s disease progressed while their testosterone remained at castration levels during the study. This analysis is called castration resistance-free survival (CRFS) and compared men receiving relugolix or leuprolide in two populations: the group of individuals with metastatic disease (or disease that has progressed beyond the prostate) and the overall group of individuals enrolled in the study (that is those with and those without metastatic disease). This analysis showed that CRFS for relugolix and the standard-of-care leuprolide were the same in the population of men with metastatic disease as well as in the overall population of the HERO study. ABSTRACT: Background: Relugolix is an oral GnRH receptor antagonist approved for men with advanced prostate cancer. Relugolix treatment has demonstrated an ability to lower testosterone to sustained castration levels in the phase 4 HERO study. Herein, we describe the results of a secondary endpoint of castration resistance-free survival (CRFS) during 48 weeks of treatment and profile patients with castration-resistant prostate cancer (CRPC). Methods: Subjects were 2:1 randomized to either relugolix 120 mg orally once daily (after a single 360 mg loading dose) or 3-monthly injections of leuprolide for 48 weeks. CRFS, defined as the time from the date of first dose to the date of confirmed prostate-specific antigen progression while castrated or death due to any reason was conducted in the metastatic disease population and the overall modified intention-to-treat (mITT) populations. Results: The CRFS analysis (mITT population) included 1074 men (relugolix: n = 717; leuprolide: n = 357) with advanced prostate cancer as well as 434 men (relugolix: n = 290; leuprolide: n = 144) with metastatic prostate cancer. In the metastatic disease populations, CRFS rates 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) at week 48. Results in the overall mITT population were similar to the metastatic population. No new safety findings were identified. Conclusions: In men with metastatic disease or in the overall population of the HERO study, CRFS assessed during the 48-week treatment with relugolix was not significantly different than standard-of-care leuprolide. Relugolix had similar efficacy for men with/without CRFS progression events.