NCT04975308: A Study of Imlunestrant, Investigator's Choice of Endocrine Therapy, and Imlunestrant Plus Abemaciclib in Participants With ER+, HER2- Advanced Breast Cancer (EMBER-3) Official Title: A Phase 3, Randomized, Open-Label Study of Imlunestrant, Investigator's Choice of Endocrine Therapy, and Imlunestrant Plus Abemaciclib in Patients With Estrogen Receptor Positive, HER2 Negative Locally Advanced or Metastatic Breast Cancer Previously Treated With Endocrine Therapy GS1-01: Imlunestrant, an Oral Selective Estrogen Receptor Degrader (SERD), as Monotherapy and Combined with Abemaciclib, for Patients with ER+, HER2- Advanced Breast Cancer (ABC), Pretreated with Endocrine Therapy (ET): Results of the Phase 3 EMBER-3 trial.
英鲁奈司群：331例 标准单药内分泌治疗：330例（其中氟维司群292例） 英鲁奈司群＋阿贝西利：213例
中位无进展生存：5.5个月比3.8个月 由于存在非比例风险证据，估计受限平均生存19.4个月 中位无进展生存：7.9个月比5.4个月（95%置信区间：6.8～9.1、4.6～6.2） 受限平均生存相差：2.6个月（95%置信区间：1.2～3.9，P<0.001） 18个月估计总生存率：77.0%比58.6%（95%置信区间：67.4～84.1、47.2～68.3） 死亡风险比：0.55（95%置信区间：0.35～0.86，P=0.008，未低于预设2.2×10-10）
中位无进展生存：5.6个月比5.5个月 进展或死亡风险比：0.87（95%置信区间：0.72～1.04，P=0.12） 18个月估计总生存率：78.6%比71.8%（95%置信区间：72.6～83.5、65.4～77.2） 死亡风险比：0.69（95%置信区间：0.50～0.96，未进行统计学检验）
中位无进展生存：9.4个月比5.5个月 进展或死亡风险比：0.57（95%置信区间：0.44～0.73，P<0.001）
中位无进展生存：9.1个月比3.7个月 进展或死亡风险比：0.51（95%置信区间：0.38～0.68，未进行统计学检验）
N Engl J Med. 2024 Dec 11. IF: 96.2
Imlunestrant with or without Abemaciclib in Advanced Breast Cancer.
Jhaveri KL, Neven P, Casalnuovo ML, Kim SB, Tokunaga E, Aftimos P, Saura C, O'Shaughnessy J, Harbeck N, Carey LA, Curigliano G, Llombart-Cussac A, Lim E, García Tinoco ML, Sohn J, Mattar A, Zhang Q, Huang CS, Hung CC, Martinez Rodriguez JL, Ruíz Borrego M, Nakamura R, Pradhan KR, Cramer von Laue C, Barrett E, Cao S, Wang XA, Smyth LM, Bidard FC; EMBER-3 Study Group.
Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York; University Hospitals Leuven, Leuven, Belgium; Hospital María Curie, Buenos Aires; Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea; National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan; Institut Jules Bordet, Hopital Universitaire de Bruxelles, Brussels; Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, Barcelona; Baylor University Medical Center, Texas Oncology, U.S. Oncology, Dallas; the Breast Center, Comprehensive Cancer Center Munich, Ludwig Maximilians University Munich University Hospital, Munich, Germany; the University of North Carolina at Chapel Hill, Chapel Hill; the University of Milan, Milan; the European Institute of Oncology, IRCCS, Milan; Hospital Arnau de Vilanova, Valencia, Spain; Garvan Institute of Medical Research and University of New South Wales, Sydney; Hospital de Oncología, Centro Médico Nacional Siglo XXI, Mexico City; Yonsei University College of Medicine, Seoul, South Korea; Women's Health Hospital, Sao Paulo; Harbin Medical University Cancer Hospital, Harbin, China; National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei; Taichung Veterans General Hospital, Taichung, Taiwan; Filios Alta Medicina, Monterrey, Mexico; Hospital Universitario Virgen del Rocío, Seville, Spain; Chiba Cancer Center Hospital, Chiba, Japan; Eli Lilly, Indianapolis; Institut Curie and University of Versailles Saint-Quentin-en-Yvelines-Paris-Saclay University, Paris.
BACKGROUND: Imlunestrant is a next-generation, brain-penetrant, oral selective estrogen-receptor (ER) degrader that delivers continuous ER inhibition, even in cancers with mutations in the gene encoding ERα (ESR1).
METHODS: In a phase 3, open-label trial, we enrolled patients with ER-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer that recurred or progressed during or after aromatase inhibitor therapy, administered alone or with a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor. Patients were assigned in a 1:1:1 ratio to receive imlunestrant, standard endocrine monotherapy, or imlunestrant-abemaciclib. Primary end points were investigator-assessed progression-free survival with imlunestrant as compared with standard therapy among patients with ESR1 mutations and among all patients and with imlunestrant-abemaciclib as compared with imlunestrant among all patients who had undergone randomization concurrently.
RESULTS: Overall, 874 patients underwent randomization, with 331 assigned to imlunestrant, 330 to standard therapy, and 213 to imlunestrant-abemaciclib. Among 256 patients with ESR1 mutations, the median progression-free survival was 5.5 months with imlunestrant and 3.8 months with standard therapy. The estimated restricted mean survival time at 19.4 months was 7.9 months (95% confidence interval [CI], 6.8 to 9.1) with imlunestrant and 5.4 months (95% CI, 4.6 to 6.2) with standard therapy (difference, 2.6 months; 95% CI, 1.2 to 3.9; P<0.001). In the overall population, the median progression-free survival was 5.6 months with imlunestrant and 5.5 months with standard therapy (hazard ratio for progression or death, 0.87; 95% CI, 0.72 to 1.04; P = 0.12). Among 426 patients in the comparison of imlunestrant-abemaciclib with imlunestrant, the median progression-free survival was 9.4 months and 5.5 months, respectively (hazard ratio, 0.57; 95% CI, 0.44 to 0.73; P<0.001). The incidence of grade 3 or higher adverse events was 17.1% with imlunestrant, 20.7% with standard therapy, and 48.6% with imlunestrant-abemaciclib.
CONCLUSIONS: Among patients with ER-positive, HER2-negative advanced breast cancer, treatment with imlunestrant led to significantly longer progression-free survival than standard therapy among those with ESR1 mutations but not in the overall population. Imlunestrant-abemaciclib significantly improved progression-free survival as compared with imlunestrant, regardless of ESR1-mutation status.
Funded by Eli Lilly
EMBER-3 ClinicalTrials.gov number, NCT04975308.
PMID: 39660834
DOI: 10.1056/NEJMoa2410858
