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.
Keywords: advanced prostate cancer; castration resistance-free survival; leuprolide; relugolix.