Abstract 621P
Background
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 LEU in the HERO study (Shore N, 2020 NEJM 382;23). A subgroup analysis was undertaken to further evaluate relugolix treatment for various clinical subgroups included in the HERO study.
Methods
The phase III HERO study was designed to evaluate relugolix in men with APC. 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 (RELAPSE), newly diagnosed androgen-sensitive metastatic disease (METASTATIC), or advanced localized disease (ALD).
Results
Of the 930 men (relugolix: 622; LEU: 308) who received study drug, 467 (50.2%), 211 (22.7%), and 252 (27.1%) men were enrolled with RELAPSE, METASTATIC, and ALD, respectively. 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 LEU groups were 9.4% (95% CI:3.6%, 15.2%) in men with RELAPSE, 11.3% (95% CI: 2.7%, 19.9%) in METASTATIC, and 2.1% (95% CI: -3.4%, 7.6%) in ALD disease. The incidence of grade ≥3 adverse events were higher in ALD for the LEU group vs relugolix group (relugolix: 13.4%; LEU: 22.5%). The incidence of grade ≥3 adverse events was higher overall in METASTATIC men (relugolix: 26.2%; LEU: 28.6%) vs the overall population (relugolix: 18.0%; LEU: 20.5%), as expected.
Conclusions
Treatment with relugolix was associated with improved castrations rates vs LEU in men with a broad range of clinical presentations for APC. Treatments were well-tolerated across the subgroups analyzed, with higher rates of grade ≥3 adverse events in men in the METASTATIC group.
Clinical trial identification
NCT03085095.
Editorial acknowledgement
Medical writing assistance was provided by JD Cox of Mayville Medical Communications and was funded by Myovant Sciences GmbH, in collaboration with Pfizer, Inc.
Legal entity responsible for the study
Myovant Sciences GmbH.
Funding
Myovant Sciences GmbH, in collaboration with Pfizer, Inc.
Disclosure
N.D. Shore: Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Institutional, Research Grant: Amgen; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Institutional, Research Grant: Astellas; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Personal, Advisory Board: Dendreon; Financial Interests, Institutional, Research Grant: Dendreon; Financial Interests, Personal, Advisory Board: Ferring; Financial Interests, Institutional, Research Grant: Ferring; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Institutional, Research Grant: Janssen; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Personal, Advisory Board: Sanofi-Genzyme; Financial Interests, Institutional, Research Grant: Sanofi-Genzyme; Financial Interests, Personal, Advisory Board: Tolmar; Financial Interests, Institutional, Research Grant: Tolmar; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Personal, Advisory Board: Myovant; Financial Interests, Institutional, Research Grant: Myovant; Financial Interests, Personal, Advisory Board: Nymax; Financial Interests, Institutional, Research Grant: Nymax. F. Saad: Financial Interests, Personal, Advisory Role: Sanofi; Financial Interests, Personal, Advisory Role: AbbVie; Financial Interests, Personal, Advisory Role: Astellas; Financial Interests, Personal, Advisory Role: Janssen; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Takeda. D.J. George: Financial Interests, Institutional, Research Grant: Acerta; Financial Interests, Personal, Advisory Role: Astellas; Financial Interests, Institutional, Research Grant: Astellas; Financial Interests, Personal, Advisory Role: Axess Oncology; Financial Interests, Personal, Speaker’s Bureau: Bayer; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Other: Calithera; Financial Interests, Personal, Advisory Board: Capio Biosciences; Financial Interests, Personal, Advisory Role: EMD Serona; Financial Interests, Personal, Advisory Role: Exelixis; Financial Interests, Personal, Speaker’s Bureau: Exelixis; Financial Interests, Personal, Advisory Role: Flatiron; Financial Interests, Personal, Advisory Role: Ipsen; Financial Interests, Personal, Advisory Role: Janssen; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Board: Modra; Financial Interests, Personal, Advisory Role: Myovant; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Nektar; Financial Interests, Personal, Advisory Role: Sanofi; Financial Interests, Personal, Speaker’s Bureau: Sanofi; Financial Interests, Personal, Advisory Role: UroToday; Financial Interests, Personal, Advisory Role: Vizuri; Financial Interests, Personal, Advisory Role: Platform Q. M.S. Cookson: Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Personal, Advisory Board: Ferring; Financial Interests, Personal, Advisory Role: Myovant; Financial Interests, Personal, Advisory Board: MDxHealth; Financial Interests, Institutional, Research Grant: MDxHealth; Financial Interests, Personal, Advisory Role: TesoRx; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Institutional, Research Grant: Medpace; Financial Interests, Institutional, Research Grant: Quintiles; Financial Interests, Institutional, Research Grant: Kantar Health; Financial Interests, Personal, Advisory Role: Altor BioScience; Financial Interests, Personal, Advisory Role: Photocure; Financial Interests, Personal, Advisory Role: Pacific Edge Diagnostics; Financial Interests, Personal, Advisory Role: Genomic Health; Financial Interests, Institutional, Research Grant: Genomic Health; Financial Interests, Personal, Advisory Role: Precision Biopsy; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Role: Astellas; Financial Interests, Institutional, Research Grant: Advanatagene; Financial Interests, Institutional, Research Grant: Dendreon; Financial Interests, Institutional, Research Grant: FKD Therapies; Financial Interests, Personal, Advisory Role: Cancer Expert Now. R. Tutrone: Financial Interests, Personal, Advisory Role: Myovant; Financial Interests, Personal, Speaker’s Bureau: Astellas; Financial Interests, Personal, Speaker’s Bureau: Pfizer; Financial Interests, Personal, Advisory Role: Nymax. B. Brown: Financial Interests, Personal, Full or part-time Employment: Myovant. B. Selby: Financial Interests, Personal, Full or part-time Employment: Myovant. S. Lu: Financial Interests, Personal, Full or part-time Employment: Myovant. J. Walling: Financial Interests, Personal, Advisory Role: Aduro; Financial Interests, Personal, Advisory Role: Arch Oncology; Financial Interests, Personal, Advisory Role: CytomX; Financial Interests, Personal, Advisory Role: Harpoon; Financial Interests, Personal, Advisory Role: ImmuNext; Financial Interests, Personal, Advisory Role: Nurix; Financial Interests, Personal, Advisory Role: Plexxikon; Financial Interests, Personal, Advisory Role: Que Oncology; Financial Interests, Personal, Advisory Role: Sesen Bio; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: Aminex; Financial Interests, Personal, Advisory Role: Crown Bio; Financial Interests, Personal, Advisory Role: Leap; Financial Interests, Personal, Advisory Role: Prothena; Financial Interests, Personal, Advisory Role: Puma; Financial Interests, Personal, Advisory Role: Rhizen; Financial Interests, Personal, Advisory Role: Shanghai Pharmaceuticals; Financial Interests, Personal, Advisory Role: Stealth; Financial Interests, Personal, Advisory Role: Sunesis; Financial Interests, Personal, Advisory Role: Upsher-Smith; Financial Interests, Personal, Advisory Role: Flag; Financial Interests, Personal, Advisory Role: Myovant. B. Tombal: Financial Interests, Personal, Principal Investigator: Myovant; Financial Interests, Institutional, Research Grant: Astellas; Financial Interests, Personal, Speaker’s Bureau: Astellas; Financial Interests, Personal, Advisory Role: Astellas; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Advisory Role: Janssen; Financial Interests, Institutional, Research Grant: Janssen; Financial Interests, Institutional, Research Grant: Ferring; Financial Interests, Personal, Advisory Role: Ferring; Financial Interests, Personal, Speaker’s Bureau: Ferring; Financial Interests, Personal, Advisory Role: Sanofi; Financial Interests, Personal, Speaker’s Bureau: Sanofi; Financial Interests, Institutional, Research Grant: Sanofi; Financial Interests, Personal, Speaker’s Bureau: Bayer; Financial Interests, Personal, Speaker’s Bureau: Janssen. All other authors have declared no conflicts of interest.