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

Neven P, Stahl N, Vidal M, Martín M, Kaufman PA, Harbeck N, Hunt KK, Carter S, Bidard FC, Fasching P, Aftimos P, Wheatley D, Hamilton E, Aft R, Kulkarni S, Schmid P, Bhave M, Ismail-Khan R, Karacsonyi C, Estrem ST, Nguyen B, Ozbek U, Yuen E, Rodrik-Outmezguine V, Ciruelos E (2024)

Publication Type: Journal article

Publication year: 2024

Journal

Book Volume: 30

Pages Range: 5304-5313

Journal Issue: 23

DOI: 10.1158/1078-0432.CCR-24-2113

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.

Authors with CRIS profile

Involved external institutions

Sarah Cannon Research Institute (SCRI) United States (USA) (US) Washington University in St. Louis United States (USA) (US) Northwestern University United States (USA) (US) Queen Mary University of London United Kingdom (GB) Emory University United States (USA) (US) Eli Lilly and Company United States (USA) (US) Hospital Universitario 12 de Octubre Spain (ES) Hospital Clínic de Barcelona Spain (ES) Katholieke Universiteit Leuven (KUL) / Catholic University of Leuven Belgium (BE) HELIOS Kliniken Germany (DE) IiSGM / Instituto de Investigación Sanitaria Gregorio Marañón Spain (ES) University of Vermont United States (USA) (US) Klinikum der Universität München Germany (DE) University of Texas MD Anderson Cancer Center United States (USA) (US) Baylor College of Medicine United States (USA) (US) Université Paris-Saclay France (FR) Institut Jules Bordet Belgium (BE) Royal Cornwall Hospital / Treliske Hospital United Kingdom (GB)

How to cite

APA:

Neven, P., Stahl, N., Vidal, M., Martín, M., Kaufman, P.A., Harbeck, N.,... Ciruelos, E. (2024). 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. Clinical Cancer Research, 30(23), 5304-5313. https://doi.org/10.1158/1078-0432.CCR-24-2113

MLA:

Neven, Patrick, et al. "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." Clinical Cancer Research 30.23 (2024): 5304-5313.

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