ASCO GU 2021: The Impact of Concomitant Prostate Cancer Therapy on Efficacy and Safety of Relugolix vs Leuprolide in Men With Advanced Prostate Cancer: Subgroup Analysis, the Phase III HERO Study

( At the 2021 American Society of Clinical Oncology Genitourinary Cancers annual meeting (ASCO GU), Dr. Daniel George and colleagues presented a subgroup analysis assessing the impact of concomitant prostate cancer therapy on the safety and efficacy of the oral GnRH receptor antagonist relugolix versus leuprolide in men with advanced prostate cancer. In the phase 3 HERO study,1 relugolix demonstrated suppression of testosterone to castrate levels in 96.7% of patients, which was superior to leuprolide, with a 54% lower risk of major adverse cardiovascular events relative to leuprolide. Relugolix is a first-in-class Federal Drug Administration (FDA) approved, oral, highly selective, GnRH receptor antagonist that is given once daily with an effective half-life of 25 hours. To characterize the impact of concomitant prostate cancer treatments with the use of relugolix in advanced prostate cancer from the HERO study, a subgroup analysis for patients receiving various therapies was undertaken. The HERO study allowed concomitant treatments in patients who developed disease progression within the 48-week treatment period. 

The HERO study was designed to evaluate relugolix in men with advanced prostate cancer. There were 934 patients randomized 2:1 to receive relugolix 120 mg orally once daily or leuprolide injections every 12 weeks for 48 weeks. In the setting of rising PSA, patients could receive enzalutamide or docetaxel two months after study initiation. Additionally, radiation therapy was allowed after two months of ADT. Assessments included sustained testosterone suppression to castrate levels (<50 ng/dL) through 48 weeks and safety parameters. Subgroups analyzed included patients with or without concomitant enzalutamide, docetaxel, and any radiation therapy. A sensitivity analysis of the primary endpoint was performed excluding patients who received concomitant therapies that may affect testosterone. As follows is the HERO trial design:


Overall, 125 patients (13.4%) took at least one concomitant therapy that could impact testosterone levels (5.0% in the relugolix group and 30.5% in the leuprolide group). Radiation therapy was received by 15.9% and 18.8% of patients in the relugolix and leuprolide groups, respectively. Enzalutamide was the most frequently used therapy in the relugolix group (2.7%), with similar use in the leuprolide group (1.9%), whereas docetaxel was used by 1.3% of patients in the relugolix group and 1.6% of patients in the leuprolide group. All other relevant concomitant therapy was used in <1% of the population, except for bicalutamide, which was used in 26.6% of patients in the leuprolide group for flare protection.  Mean duration for enzalutamide was 13.9 weeks (SD 10.4 weeks) in the relugolix group and 14.0 weeks (SD 10.9 weeks) in the leuprolide groups. The mean duration for docetaxel was 7.0 21-day cycles (SD 5.7) in the relugolix group and 10.2 21-day cycles (SD 11.0) in the leuprolide group. The estimated castration rates for the sensitivity analysis excluding patients who received concomitant therapies that may affect testosterone levels was 96.9% (95% CI 95.0% to 98.1%) for relugolix for 48 weeks compared with 89.6% (95% CI 84.6% to 93.0%) for leuprolide (between group difference: 7.3%, 95% CI 2.9% to 11.7%). Castration rates were similar with and without concomitant use of enzalutamide and docetaxel or radiation therapy:


No clinically relevant differences in adverse events were observed between patients with or without concomitant use of enzalutamide, docetaxel or radiation therapy in either treatment group.

Dr. George concluded this subgroup analysis of the HERO trial with the following take-home points:

  • While the numbers are small, treatment with relugolix was associated with a similar efficacy and safety profiles in patients who received concomitant administration of enzalutamide, docetaxel, or radiation therapy to that observed in patients not receiving those concomitant treatments
  • Overall incidence of adverse events was similar between relugolix and leuprolide in patients with or without concomitant therapy
  • Standard of care use of concomitant relugolix and radiation therapy is supported by this data
  • Further prospective studies are justified combining relugolix with concomitant enzalutamide, docetaxel and other systemic treatment options


Presented by: Daniel J. George, MD, Duke Cancer Institute Center for Prostate and Urologic Cancers, Duke University, Durham, NC

Co-Authors: Neal D. Shore, Fred Saad, Michael Cookson, Daniel Saltzstein, Ronald F. Tutrone, Hideyuki Akaza, Alberto Bossi, Elaine K. Wong, Bryan Selby, Xiaolin Fan, Jackie Walling, Bertrand Tombal; Carolina Urologic Research Center, Myrtle Beach, SC; Centre Hospitalier de l’Université de Montréal, Montréal, QC, Canada; University of Oklahoma Health Sciences Center, Oklahoma City, OK; Urology San Antonio, San Antonio, TX; Chesapeake Urology, Towson, MD; The University of Tokyo, Tokyo, Japan; Gustave Roussy Institute, Villejuif, France; Myovant Sciences, Inc, Brisbane, CA; Myovant Sciences, Brisbane, CA; Myovant Sciences, Inc., Brisbane, CA; Institut de Recherche Clinique, Université Catholique de Louvain, Louvain, Belgium

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, Twitter: @zklaassen_md during the 2021 ASCO Genitourinary Cancers Symposium (ASCO GU), February 11th to 13th, 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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