A Preoperative Window-of-Opportunity Study of Oral SERD, Imlunestrant, in Newly Diagnosed ER-Positive, HER2-Negative Early Breast Cancer: Results from the EMBER-2 Study
Year: 2024
Type: article
Abstract: PURPOSE: Imlunestrant is an oral selective estrogen receptor degrader with favorable safety and preliminary efficacy in patients with advanced breast cancer. Pharmacodynamic (PD) biomarker data can optimize drug dosing; in this study, we present PD data from the EMBER-2 study. PATIENTS AND METHODS: Postmenopausal women with untreated, operable estrogen receptor (ER)-positive, HER2-negative early breast cancer were randomized to 400 versus 800 mg of imlunestrant daily for ∼2 weeks before surgery. A single arm study tested a daily dose of 200 mg. PD biomarker changes (ER, progesterone receptor, Ki-67 by IHC, and mRNA expression of ER-related genes) were evaluated in paired tumor samples (pre-/posttreatment). Safety and pharmacokinetics were also assessed. RESULTS: Among evaluable paired samples (n = 75), PD profiles demonstrated consistent ER targeting between 400- and 800-mg doses, with less toxicity at the 400-mg dose. Although inducing the lowest rate of complete cell-cycle arrest, PD and pharmacokinetic results were similar for the 200-mg dose. CONCLUSIONS: EMBER-2 combined with existing phase I data has identified 400 mg as the optimal imlunestrant dose.
Source: Clinical Cancer Research
Authors: Patrick Neven, Nicole Stahl, Maria Vidal, Miguel Martín, Peter A. Kaufman, Nadia Harbeck, Kelly K. Hunt, Stacey Carter, Francois-Clement Bidard, Peter A. Fasching, Philippe Aftimos, Duncan Wheatley, Erika Hamilton, Rebecca Aft, Swati Kulkarni, Peter Schmid, Manali Bhave, Roohi Ismail-Khan, Claudia Karacsonyi, Shawn T. Estrem, Bastien Nguyen, Umut Ozbek, Eunice Yuen, Vanessa Rodrik-Outmezguine, Eva Ciruelos
Institutions: Universitair Ziekenhuis Leuven, Helios Hospital Schwerin, Hospital Clínic de Barcelona, Consorci Institut D'Investigacions Biomediques August Pi I Sunyer, Universitat de Barcelona, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, University of Vermont, University of Vermont Medical Center, LMU Klinikum, Ludwig-Maximilians-Universität München, The University of Texas MD Anderson Cancer Center, Baylor College of Medicine, Dan L Duncan Comprehensive Cancer Center, Université Paris-Saclay, Institut Curie, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, Comprehensive Cancer Center Erlangen, Université Libre de Bruxelles, Institut Jules Bordet, Royal Cornwall Hospital Trust, Royal Cornwall Hospital, Sarah Cannon, Tennessee Oncology, Washington University in St. Louis, Northwestern University, Queen Mary University of London, Barts Cancer Institute, Emory University, Winship Cancer Institute, Eli Lilly (United States), Memorial Sloan Kettering Cancer Center, Hospital Universitario 12 De Octubre, HM Hospitales
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Funder: Eli Lilly and Company
OpenAlex ID: W4403222442