ASCO 2021: Impact of Age on Efficacy and Safety of Relugolix: A Subgroup Analysis from the Randomized, Phase 3 HERO Study Versus Leuprolide in Men with Advanced Prostate Cancer

( Androgen deprivation therapy (ADT) is a cornerstone of prostate cancer treatment and is usually achieved with luteinizing hormone-releasing hormone (LHRH) agonists or gonadotropin-releasing hormone (GnRH) antagonists. Relugolix is a first-in-class FDA-approved, oral, highly selective, GnRH receptor antagonist that is given once daily with an effective half-life of 25 hours for the treatment of adult men with advanced prostate cancer.  In the phase 3 HERO study, relugolix demonstrated sustained testosterone suppression to castrate levels in 96.7% of men, superior to that of leuprolide, and a comparative 54% decrease in risk of major adverse cardiovascular events.1 The HERO study included men with a broad range of ages, with a median of 71 and a range from 47 to 97 years of age. Dr. Michael Cookson and colleagues at the 2021 American Society of Clinical Oncology (ASCO) 2021 Annual Meeting, Dr. Michael Cookson presented the results of their study further characterizing the impact of age on the use of relugolix in advanced prostate cancer from the HERO study.

The HERO study was a randomized, open-label, parallel-group study evaluating relugolix in men with advanced prostate cancer. Overall, 934 men with advanced prostate cancer underwent 2:1 randomization to receive relugolix 120 mg orally once daily after a single loading dose of 360 mg or leuprolide 3-month injections for 48 weeks. Subgroups analyzed by age were <65 years or ≥65 years and ≤75 years or >75 years. Assessments analyzed included:

  • Sustained testosterone suppression to castrate levels (<50 ng/dL) from day 29 through 48 weeks
  • Early and profound (<20 ng/dL) castration rates
  • PSA levels
  • Safety
Testosterone recovery (≥280 ng/dL) was also evaluated in 184 patients who enrolled in the testosterone recovery substudy. Of the 930 patients (relugolix: n = 622; leuprolide: n = 308) that received study drug in the HERO study, 173 (18.6%) were <65 years and 757 (81.4%) were ≥65 years of age, while 664 (71.4%) were ≤75 years and 266 (28.6%) were >75 years of age. Across all age subgroups, point estimates for sustained castration rates through 48 weeks for relugolix patients were consistent with the overall estimate of relugolix sustained castration rate observed in the overall population:


Differences in sustained castrations rates at week 48 between relugolix and leuprolide groups were similar regardless of the age subgroup:


The subgroup results by age from the secondary endpoints were also generally consistent with the results in the overall population:


The likelihood of testosterone recovery at 90 days after completion of treatment was higher in the relugolix group versus the leuprolide group in all age subgroups: <65 (79.1% vs 16.7%), ≥65 (48.6% vs 0%), ≤75 (60.0% vs 4.0%), and >75 years (40.7% vs 0%):


In general, the safety profile of relugolix was consistent across all age groups for both drugs. Furthermore, no clinically relevant differences were noted in the incidence or types of adverse events within treatment groups in all the age subgroups analyzed.

Dr. Cookson concluded this presentation of age as a subgroup analysis for the HERO phase 3 trial with the following concluding statements:

  • In this subgroup analysis of the HERO study, relugolix was effective regardless of age, and the benefit/risk profile remained favorable for relugolix compared with leuprolide, consistent with the overall population
  • Consistent improvement in sustained castration rates with relugolix over leuprolide was observed at week 48 in all age subgroups
  • Testosterone recovery was higher in the relugolix group than the leuprolide group for all age subgroups analyzed, with higher rates of recovery in younger versus older men

Clinical trial information: NCT03085095

Presented by: Michael Cookson, MD, MMHC, University of Oklahoma Health Sciences Center, Stephenson Cancer Center, Oklahoma City, OK

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia Twitter: @zklaassen_md at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, Virtual Annual Meeting #ASCO21, June, 4-8, 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.