ESMO 2021: Geographical Assessment of Efficacy and Safety of Relugolix: A Subgroup Analysis from the Randomized, Phase 3 HERO Study vs Leuprolide in Men with Advanced Prostate Cancer

( The European Society of Medical Oncology (ESMO) 2021 annual meeting’s prostate cancer session included a presentation by Dr. Bertrand Tombal discussing a subgroup analysis of the phase 3 HERO study assessing geographical efficacy and safety of relugolix versus leuprolide among men with advanced prostate cancer. Androgen deprivation therapy is a cornerstone of prostate cancer treatment and is usually given with gonadotropic-releasing hormone (GnRH) agonists or GnRH receptor antagonists. Relugolix, the once-daily oral GnRH receptor antagonist, demonstrated suppression of testosterone to castrate levels in 96.7% of patients, and a 54% lower risk of major adverse cardiovascular events relative to leuprolide in the HERO study.1 At the ESMO 2021 meeting, Dr. Tombal and colleagues presented results characterizing the geographical impact on the efficacy and safety of relugolix versus leuprolide in advanced prostate cancer, a subgroup analysis of HERO was undertaken.

HERO was a phase III randomized, open-label, study to evaluate relugolix versus leuprolide in 930 men with advanced prostate cancer. Men were randomized 2:1 to receive relugolix or leuprolide for 48 weeks. Subgroups analyzed for geography were North and South America, the United States only, Europe, and Asia Pacific. Assessments analyzed included sustained testosterone suppression to castrate levels (<50 ng/dL) through 48 weeks, early and profound castration rates (<20 ng/dL), PSA levels, and safety.

Of the 930 men (relugolix: 622; leuprolide: 308) enrolled in HERO, 322 (34.6%) were enrolled from North and South America, 225 (24.5%) from the United States alone, 369 (39.7%) from Europe, and 239 (25.7%) men were enrolled from Asia Pacific. In all geographical subgroups, point estimates for sustained castration rates for men receiving relugolix were consistent with the overall estimate of relugolix sustained castration rate observed in the overall population:

ESMO HERO-0.jpg 

Similar results were noted for profound castration rates: 

ESMO HERO-1.jpg  

No clinically relevant differences were noted in the incidence or types of adverse events within treatment groups in the subgroups analyzed:  

ESMO HERO-2.jpg  

Fewer men in the relugolix group versus the leuprolide group had at least one major adverse cardiovascular event in North and South America (3.7% vs 5.7%), the United States alone (3.8% vs 7.2%), Europe (2.4% vs 6.6%), and Asia Pacific (2.5% vs 6.3%).

Dr. Tombal concluded his presentation assessing geography as a subgroup analysis of the phase 3 HERO trial with the following take-home messages:

  • In this HERO study subgroup analysis, relugolix was well tolerated and effective across all geographical locations of men
  • These results are consistent with those of the overall population where relugolix achieved rapid, sustained suppression of testosterone levels that was superior to that with leuprolide, with a similar overall safety and tolerability profile in the two groups

Presented by: Bertrand Tombal, MD, PhD, Urology, Cliniques universitaires Saint-Luc, UC Louvain, Brussels, Belgium

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2021 European Society for Medical Oncology (ESMO) Annual Congress 2021, Thursday, Sep 16, 2021 – Tuesday, Sep 21, 2021.


  1. Shore ND, Saad F, Cookson MS, et al. Oral Relugolix for Androgen-Deprivation Therapy in Advanced Prostate Cancer. N Engl J Med. 2020 Jun 4;382(23):2187-2196.
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