FDA approves combo for ESR1-mutated breast cancer

In an exploratory subgroup analysis of patients with ESR1-mutated tumors, median progression-free survival was 11.1 months with the combination and 5.5 months with imlunestrant alone.

By
Kathryn Wighton
September 21, 2026
2 min

MDSpire News

Objective:

To evaluate the efficacy of imlunestrant with abemaciclib in adults with ESR1-mutated advanced or metastatic breast cancer.

Approach:

Study Design: The EMBER-3 trial was a randomized, open-label, active-controlled, multicenter study involving 874 adults with estrogen receptor-positive, HER2-negative locally advanced or metastatic breast cancer.
Patient Selection: Patients had previously received an aromatase inhibitor alone or with a CDK4/6 inhibitor and were randomly assigned to receive imlunestrant, investigator-selected endocrine therapy, or imlunestrant plus abemaciclib.
Mutation Detection: The Guardant360 CDx assay was used to assess circulating tumor DNA for ESR1 mutations.

Key Findings:

Imlunestrant plus abemaciclib showed statistically significant improvement in progression-free survival compared to imlunestrant monotherapy.
In patients with ESR1-mutated tumors, median progression-free survival was 11.1 months with the combination therapy versus 5.5 months with imlunestrant alone.
Objective response rates were 35% for the combination therapy and 15% for imlunestrant alone.

Interpretation:

Overall survival data were immature at the interim analysis.

Limitations:

The trial excluded patients eligible for PARP inhibitor therapy.
Overall survival data were not fully mature.

Conclusion:

Imlunestrant with abemaciclib is approved for specific patients with ESR1-mutated breast cancer following disease progression after endocrine therapy.