In patients with ESR1 mutations, imlunestrant significantly improved progression-free survival compared to standard therapy. Imlunestrant–abemaciclib further improved progression-free survival compared to imlunestrant alone. Safety profiles were consistent, with higher adverse event rates in combination therapy.
Study
|
Open-label, phase 3 trial [EMBER-3; NCT04975308] |
| ER-positive, HER2-negative advanced breast cancer after aromatase inhibitor therapy |
| Imlunestrant (n=331) vs Standard therapy (n=330) vs Imlunestrant–Abemaciclib (n=213)
|
Efficacy
|
mPFS (ESR1 mutations): 5.5 mos vs 3.8 mos (imlunestrant vs. standard) |
| mPFS (overall): 5.6 mos vs 5.5 mos (HR 0.87) |
| OS @18mos (ESR1 mutated): 77% vs. 78.6% {HR: 0.55 [0.35-0.86], p=0.008) |
| OS @18mos (overall): 78.6% vs. 71.8% (HR: 0.69 [0.50-0.96])
|
Safety
|
Grade >=3 AE: 17.1% vs 20.7% vs 48.6% (imlunestrant vs. standard vs. imlunestrant + abemaciclib) |
| Serious AE: 10.4% vs 11.4% vs 16.8% |
| Treatment discontinuation: 4.3% vs 1.2% vs 6.3%
|
N Engl J Med 2025;392:1189-202
Jhaveri KL, Neven P, Casalnuovo ML New Drug: Imlunestrant for ESR1-Mutated Advanced Breast Cancer
http://doi.org/10.1056/NEJMoa2410858
Reviewed by Ulas D. Bayraktar, MD on Oct 17, 2025
