Abstract 622P
Background
In the international phase III HERO study, the once-daily oral GnRH receptor antagonist, relugolix, demonstrated superior continuous suppression of testosterone to castrate levels through week 48 compared to LEU, and a 54% lower risk of major adverse cardiovascular events relative to LEU (Shore N, 2020 NEJM 382;23). To further characterize the geographical impact on the efficacy and safety of relugolix vs LEU in APC, a subgroup analysis of HERO was undertaken.
Methods
HERO was a phase III randomized, open-label, study to evaluate relugolix vs LEU in 930 men with APC. Subgroups analyzed for geography were North and South America, United States only, Europe, and Asia Pacific. Assessments analyzed included sustained testosterone suppression to castrate levels (<50 ng/dL) through 48 weeks, early and profound castration rates (<20 ng/dL), PSA levels, and safety.
Results
Of the 930 men (relugolix:622; LEU:308) enrolled in HERO, 322 (34.6%), 225 (24.5%), 369 (39.7%), and 239 (25.7%) men were enrolled from North and South America, United States alone, Europe, and Asia Pacific, respectively. In all geographical subgroups, point estimates for sustained castration rates for men receiving relugolix were consistent with the overall estimate of relugolix sustained castration rate observed in the overall population (Table). No clinically relevant differences were noted in the incidence or types of adverse events within treatment groups in the subgroups analyzed. Table: 622P
Geographical subgroup castration rates
| North/South America | US Only | Europe | Asia Pacific | Overall Population | ||||||
| Relugolix N=216 | LEU N=106 | Relugolix N=156 | LEU N=69 | Relugolix N=247 | LEU N=122 | Relugolix N=169 | LEU N=80 | Relugolix N=622 | LEU N=308 | |
| Castration rate, % | 96.5 | 83.5 | 97.1 | 81.1 | 96.9 | 93.4 | 96.6 | 88.7 | 96.7 | 88.8 |
| Profound castration rate, % | 75.5 | 1.9 | 71.2 | 1.5 | 76.8 | 0.8 | 84.8 | 0 | 78.4 | 1.0 |
LEU = leuprolide. Castration Rate and profound castrations rate are defined as the cumulative probability of testosterone to <50 ng/dL through 48 weeks and to <20 ng/dL at day 15, respectively.
Conclusions
In this HERO study subgroup analysis, relugolix was well tolerated and effective across all geographical location of men. These results are consistent with those of the overall population where relugolix achieved rapid, sustained suppression of testosterone levels that was superior to that with LEU, with a similar overall safety and tolerability profile in the two groups.
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.
Disclosure
N.D. Shore: Financial Interests, Invited Speaker: Amgen; Financial Interests, Invited Speaker: Amgen; Financial Interests, Invited Speaker: AstraZeneca; Financial Interests, Invited Speaker: AstraZeneca; Financial Interests, Invited Speaker: Bayer; Financial Interests, Invited Speaker: 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, Project Lead: 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: Nymox; Financial Interests, Institutional, Research Grant: Nymox. R. Tutrone: Financial Interests, Personal, Stocks/Shares: Myovant; 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: Nymox. 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: TesoRx; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Role: Altor BioScience; Financial Interests, Personal, Advisory Role: Photocure; Financial Interests, Personal, Advisory Role: Pacific Edge; Financial Interests, Personal, Advisory Role: Genomic Health; Financial Interests, Personal, Advisory Role: Precision Biopsy; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Role: Astellas Pharma; Financial Interests, Institutional, Research Grant: Advanatagene; Financial Interests, Institutional, Research Grant: FKD Therapies. D.J. George: Financial Interests, Institutional, Research Grant: Acerta; Financial Interests, Institutional, Research Grant: Astellas; Financial Interests, Personal, Advisory Role: Astellas; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Axess Oncology; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Institutional, Research Grant: 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: Jannssen; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Modra; Financial Interests, Personal, Advisory Board: Myovant; Financial Interests, Personal, Other: Nektar; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Institutional, Other: Pfizer; Financial Interests, Personal, Advisory Role: Sanofi; Financial Interests, Personal, Advisory Role: Vizuri Health Sciences; Financial Interests, Personal, Advisory Role: Platform Q. 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, Other: Aduro Biotech; Financial Interests, Personal, Other: Arch Oncology; Financial Interests, Personal, Other: CytomX; Financial Interests, Personal, Other: Harpoon; Financial Interests, Personal, Other: ImmuNext; Financial Interests, Personal, Other: Nurix; Financial Interests, Personal, Other: Plexxikon; Financial Interests, Personal, Other: Que Oncology; Financial Interests, Personal, Other: Sesen Bio; Financial Interests, Personal, Other: Amgen; Financial Interests, Personal, Other: Aminex; Financial Interests, Personal, Other: Crown Bio; Financial Interests, Personal, Other: Leap; Financial Interests, Personal, Other: Prothena; Financial Interests, Personal, Other: Puma; Financial Interests, Personal, Other: Rhizen; Financial Interests, Personal, Other: Shanghai Pharmaceuticals; Financial Interests, Personal, Other: Stealth Biotherapeutics; Financial Interests, Personal, Other: Sunesis Pharmaceuticals; Financial Interests, Personal, Other: Usher-Smith; Financial Interests, Personal, Other: Flag Therapeutics; Financial Interests, Personal, Other: Myovant. B. Tombal: Financial Interests, Institutional, Principal Investigator: Myovant; Financial Interests, Personal, Speaker’s Bureau: Astellas; Financial Interests, Institutional, Principal Investigator: Astellas; Financial Interests, Personal, Speaker’s Bureau: Bayer; Financial Interests, Institutional, Principal Investigator: Bayer; Financial Interests, Personal, Speaker’s Bureau: Janssen; Financial Interests, Institutional, Principal Investigator: Janssen; Financial Interests, Personal, Advisory Role: Ferring; Financial Interests, Institutional, Research Grant: Ferring; Financial Interests, Personal, Speaker’s Bureau: Sanofi; Financial Interests, Institutional, Principal Investigator: Sanofi; Financial Interests, Personal, Advisory Board: Sanofi. 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: Takeda. All other authors have declared no conflicts of interest.