口服选择性雌激素受体降解剂（SERD）艾拉司群用于新诊断的雌激素受体阳性、人表皮生长因子受体2阴性早期乳腺癌的术前机会窗研究：EMBER-2研究结果
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.
作者信息
Neven Patrick, Stahl Nicole, Vidal Maria, Martín Miguel, Kaufman Peter A, Harbeck Nadia, Hunt Kelly K, Carter Stacey, Bidard Francois-Clement, Fasching Peter A, Aftimos Philippe, Wheatley Duncan, Hamilton Erika, Aft Rebecca, Kulkarni Swati, Schmid Peter, Bhave Manali, Ismail-Khan Roohi, Karacsonyi Claudia, Estrem Shawn T, Nguyen Bastien, Ozbek Umut, Yuen Eunice, Rodrik-Outmezguine Vanessa, Ciruelos Eva
机构信息
Leuven Cancer Institute, Universitaire Ziekenhuizen (UZ), Leuven, Belgium.
Helios Kliniken Schwerin, Schwerin, Germany.
出版信息
Clin Cancer Res. 2024 Dec 2;30(23):5304-5313. doi: 10.1158/1078-0432.CCR-24-2113.
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.
目的
Imlunestrant是一种口服选择性雌激素受体降解剂，在晚期乳腺癌患者中具有良好的安全性和初步疗效。药效学（PD）生物标志物数据可优化药物剂量；在本研究中，我们展示了EMBER-2研究的PD数据。
患者与方法
未接受治疗、可手术的雌激素受体（ER）阳性、人表皮生长因子受体2（HER2）阴性的绝经后早期乳腺癌女性患者在手术前随机分为每日服用400 mg与800 mg的Imlunestrant，持续约2周。一项单臂研究测试了每日200 mg的剂量。在配对的肿瘤样本（治疗前/后）中评估PD生物标志物变化（通过免疫组化检测ER、孕激素受体、Ki-67，以及ER相关基因的mRNA表达）。同时评估安全性和药代动力学。
结果
在可评估的配对样本（n = 75）中，PD图谱显示400 mg和800 mg剂量之间对ER的靶向作用一致，400 mg剂量的毒性较小。尽管200 mg剂量诱导完全细胞周期停滞的发生率最低，但其PD和药代动力学结果相似。
结论
EMBER-2研究结合现有的I期数据确定400 mg为Imlunestrant的最佳剂量。
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