Imlunestrant with or without Abemaciclib in Advanced Breast Cancer
Journal
New England Journal of Medicine
Series/Report No.
New England Journal of Medicine
Journal Volume
392
Journal Issue
12
Start Page
1189-1202
ISSN
0028-4793
1533-4406
Date Issued
2025-03-27
Author(s)
Jhaveri, Komal L.
Neven, Patrick
Casalnuovo, Monica Lis
Kim, Sung-Bae
Tokunaga, Eriko
Aftimos, Philippe
Saura, Cristina
O’Shaughnessy, Joyce
Harbeck, Nadia
Carey, Lisa A.
Curigliano, Giuseppe
Llombart-Cussac, Antonio
Lim, Elgene
García Tinoco, María de la Luz
Sohn, Joohyuk
Mattar, André
Zhang, Qingyuan
Hung, Chih-Chiang
Martinez Rodriguez, Jorge Luis
Ruíz Borrego, Manuel
Nakamura, Rikiya
Pradhan, Kamnesh R.
Cramer von Laue, Christoph
Barrett, Emily
Cao, Shanshan
Wang, Xuejing Aimee
Smyth, Lillian M.
Bidard, François-Clément
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.).
SDGs
Publisher
Massachusetts Medical Society
Type
journal article