ASCO 2022: Efficacy and Safety of Relugolix in Men with Advanced Prostate Cancer Based on Baseline BMI: A Subgroup Analysis from the Randomized, Phase 3 HERO Study Versus Leuprolide

( The 2022 ASCO annual meeting featured a session on prostate cancer, including a presentation by Dr. Fred Saad discussing a subgroup analysis of the HERO trial assessing the efficacy and safety of relugolix versus leuprolide in men with advanced prostate cancer based on baseline body mass index (BMI). BMI has been correlated with adverse prostate cancer outcomes, such as risk of biochemical failure, mortality, and ADT complications. However, a systematic review and meta-analysis suggested no association between BMI and prostate cancer risk, as well as improved survival in advanced prostate cancer patients with a high BMI. There is also evidence of an inverse and non-linear association between BMI and PSA, such that for overweight/obese men, this may lead to a reduced risk of being diagnosed with prostate cancer due to the role of PSA screening or testing in many prostate cancer diagnoses. Relugolix is a FDA-approved, once-daily oral GnRH receptor antagonist that has demonstrated superior continuous suppression of testosterone to castrate levels through Week 48 compared to leuprolide (96.7% vs 88.8%, respectively)1 in men with advanced prostate cancer. This HERO subgroup analysis looks at the impact of baseline BMI on efficacy and safety.

HERO was a phase 3 randomized, open-label study to evaluate relugolix vs leuprolide in 930 men with advanced prostate cancer. This analysis looked at all men enrolled and treated in the HERO study divided by baseline BMI subgroups:

  • <25.0 kg/m2: underweight and healthy weight
  • 25.0 – 29.9 kg/m2: overweight
  • >29.9 kg/m2: obese 

Assessments included sustained testosterone suppression to castrate levels (<50 ng/dL) from Day 29 through 48 weeks, early testosterone suppression to castrate levels (Day 4 and Day 15), PSA response (>50% decrease from baseline) at Day 15 with confirmation at Day 29, and profound castration rate (<20 ng/dL) at Day 15. Testosterone recovery subset analysis was not included due to low patient numbers. All analyses performed were descriptive.

Of the 930 men (relugolix: 622; leuprolide: 308) treated in HERO, 287 (30.9%) men had BMI <25 kg/m2, 424 (45.6%) were 25 – 29.9 kg/m2, 219 (23.5%) were >29.9 kg/m2. Men with higher BMI were more likely to be <=75 years of age, had lower baseline mean testosterone levels, and more likely to be North American. Sustained castration rates through 48 weeks were higher for the relugolix group than the leuprolide group across all three BMI subgroups:


Results for select key secondary endpoints were generally consistent across BMI categories, although PSA response proportions were lower in obese men:


No differences were noted in the incidence or types of adverse events within treatment groups in the subgroups analyzed. There were some variations among subgroups, such as, a decrease in grade >=3 adverse events in the lowest BMI group and increases in hot flashes and fatigue in higher BMI subgroups:


Dr. Saad concluded his presentation discussing a subgroup analysis of the HERO trial assessing the efficacy and safety of relugolix versus leuprolide in men with advanced prostate cancer based on baseline BMI with the following take-home messages:

  • In this HERO study subgroup analysis, relugolix demonstrated greater continuous testosterone suppression than leuprolide regardless of baseline BMI
  • Testosterone responses were generally similar regardless of BMI
  • A numerically lower PSA response was seen in obese patients
  • Additional research with longer follow-up is warranted

Presented by: Fred Saad, MD, FRCS, University of Montréal Health Center, Montréal, QC, Canada

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 2022 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago, IL, Fri, June 3 – Mon, June 7, 2022. 


  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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