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

(UroToday.com) 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 the 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 the results of a subgroup analysis undertaken to further evaluate relugolix treatment for various clinical subgroups included in the HERO study.

 

The phase III HERO study was designed to evaluate relugolix in men with advanced prostate cancer. Assessments included sustained testosterone suppression to castrate levels (<50 ng/dL) from day 29 through 48 weeks, early and profound castration rates, and safety parameters. Subgroups analyzed included men with 1 of 3 clinical disease presentations: biochemical (PSA) or clinical relapse following local primary intervention, newly diagnosed androgen-sensitive metastatic disease, or advanced localized disease.

 Of the 930 men (relugolix: 622; leuprolide: 308) who received study drug, 467 (50.2%) were enrolled with PSA or clinical relapse following local primary intervention, 211 (22.7%), were newly diagnosed androgen-sensitive metastatic disease, and 252 (27.1%) men were enrolled with advanced localized disease. As follows are the baseline demographics by clinical subgroups:

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Across all clinical subgroups, point estimates for sustained castration rates for men receiving relugolix were consistent with the overall sustained castration rate. Differences in sustained castrations rates at week 48 between relugolix and leuprolide groups were 9.4% (95% CI 3.6%, 15.2%) in men with PSA or clinical relapse following local primary intervention, 11.3% (95% CI 2.7%, 19.9%) in newly diagnosed androgen-sensitive metastatic disease, and 2.1% (95% CI -3.4%, 7.6%) in advanced localized disease:

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The incidence of grade ≥3 adverse events was higher in advanced localized disease for the leuprolide group versus the relugolix group (relugolix: 13.4%; leuprolide: 22.5%). The incidence of grade ≥3 adverse events was higher overall in newly diagnosed androgen-sensitive metastatic disease men (relugolix: 26.2%; leuprolide: 28.6%) versus the overall population (relugolix: 18.0%; leuprolide: 20.5%), as expected.

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Dr. Tombal concluded with the following take-home messages from this subgroup analysis of the HERO phase 3 trial:

  • Treatment with relugolix was associated with improved castrations rates versus leuprolide in men with a broad range of clinical presentations for advanced prostate cancer
  • Treatments were generally well-tolerated across the subgroups analyzed, with higher rates of grade ≥3 adverse events in men in the newly diagnosed androgen-sensitive metastatic disease group, reflective of the more advanced disease in these men


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.