AUA 2022: Oral Relugolix for Androgen Deprivation Therapy in Advanced Prostate Cancer: Detailed Safety Analysis from the Randomized Phase 3 HERO Study

( In a moderated poster presentation at the 2022 American Urologic Association Annual Meeting held in New Orleans and virtually, Dr. Shore presented a detailed safety analysis of the oral LHRH antagonist relugolix, based on data from the HERO trial. This trial, which enrolled men with advanced prostate cancer, demonstrated that relugolix, a highly selective nonpeptide oral GnRH antagonist, was well tolerated, with hot flash and fatigue as the most frequently reported adverse events (AE) for men in both relugolix and leuprolide groups. Further, in analyses of secondary endpoints, patients treated with relugolix had a 54% lower risk of major adverse cardiovascular events (MACE) compared to those receiving leuprolide. This analysis presented by Dr. Shore highlighted detailed safety analysis from the HERO study, including reviewing adverse events (AE) onset and duration data.

To summarize the previously published methodology, the phase 3 HERO study enrolled 930 men with advanced prostate cancer who were randomized in a 2:1 fashion to receive relugolix 120 mg orally once daily (after a 360 mg day 1 loading dose) or leuprolide injections every 12 weeks for 48 weeks. In terms of safety assessments, the authors examined AEs (assessed according to the National Cancer Institute Common Terminology Criteria for AEs, version 4.03), MACE (defined as nonfatal myocardial infarction, non-fatal stroke, and death from any cause), as well as onset (median days from the date of first dose to the initial event) and duration (median days from start to end date of the event) of the most common events.

The authors identified AEs in 92.9% of men in relugolix group and 93.5% in the leuprolide group. Hot flash, fatigue, constipation, diarrhea, and arthralgia were the most frequent events.


In terms of serious safety events, grade ≥3 AEs were reported in 18.0% of men receiving relugolix and 20.5% men in the leuprolide group. The most frequently reported (≥1%) grade ≥ 3 AEs (regardless of treatment allocation) included hypertension, diabetes mellitus, and syncope. All other grade ≥ 3 AEs were reported with similar incidence in both treatment groups. MACE occurred in 2.9% and 6.2% of patients on relugolix and leuprolide, respectively. Among common AEs (those occurring in ≥ 10% patients), the median time to onset was 19.0-142.0 days in the relugolix group and 41.0-188.5 days in the leuprolide group. There was notable variation in the time to onset between differing AEs. Further, the duration varied among the AEs.


Dr. Shore therefore concluded that these data demonstrate that relugolix, an oral nonpeptide GnRH receptor antagonist, was generally well tolerated in the phase 3 HERO study. Detailed analysis of the safety data suggests that AEs occur early during treatment with varying duration depending on the type of event.

Presented by: Neal D. Shore, MD, FACS is the Medical Director for the Carolina Urologic Research Center

Written by: Christopher J.D. Wallis, University of Toronto, Twitter: @WallisCJD during the 2022 American Urological Association (AUA) Annual Meeting, New Orleans, LA, Fri, May 13 – Mon, May 16, 2022.


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