Imlunestrant with or without abemaciclib in advanced breast cancer Journal Article


Authors: Jhaveri, K. L.; Neven, P.; Casalnuovo, M. L.; Kim, S. B.; Tokunaga, E.; Aftimos, P.; Saura, C.; O'Shaughnessy, J.; Harbeck, N.; Carey, L. A.; Curigliano, G.; Llombart-Cussac, A.; Lim, E.; García Tinoco, M. L.; Sohn, J.; Mattar, A.; Zhang, Q.; Huang, C. S.; Hung, C. C.; Martinez Rodriguez, J. L.; Ruíz Borrego, M.; Nakamura, R.; Pradhan, K. R.; Cramer von Laue, C.; Barrett, E.; Cao, S.; Wang, X. A.; Smyth, L. M.; Bidard, F. C.; for the EMBER-3 Study Group
Article Title: Imlunestrant with or without abemaciclib in advanced breast cancer
Abstract: 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.). Copyright © 2024 Massachusetts Medical Society.
Keywords: adult; controlled study; aged; aged, 80 and over; middle aged; genetics; mutation; clinical trial; mortality; comparative study; antineoplastic agent; progression free survival; randomized controlled trial; antineoplastic combined chemotherapy protocols; epidermal growth factor receptor 2; aromatase inhibitor; pathology; breast neoplasms; multicenter study; breast tumor; receptor, erbb-2; phase 3 clinical trial; antineoplastic agents, hormonal; drug therapy; estradiol; aromatase inhibitors; antineoplastic hormone agonists and antagonists; benzimidazole derivative; benzimidazoles; cyclin dependent kinase 4; cyclin-dependent kinase 4; cyclin dependent kinase 6; progression-free survival; cyclin-dependent kinase 6; estrogen receptor alpha; very elderly; humans; human; female; abemaciclib; aminopyridines; aminopyridine derivative; esr1 protein, human
Journal Title: New England Journal of Medicine
Volume: 392
Issue: 12
ISSN: 0028-4793
Publisher: Massachusetts Medical Society  
Date Published: 2025-03-27
Start Page: 1189
End Page: 1202
Language: English
DOI: 10.1056/NEJMoa2410858
PUBMED: 39660834
PROVIDER: scopus
DOI/URL:
Notes: Article -- Source: Scopus
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  1. Komal Lachhman Jhaveri
    215 Jhaveri