Imlunestrant with or without Abemaciclib in Advanced Breast Cancer
- Study type
- Clinical trial
- Study name
- EMBER-3
- Phase
- Phase 3
- Design
- Randomised open-label trial with 1:1:1 allocation to three groups
- Sample size
- 874 patients
- Source
- N Engl J Med · 2025
- Trial registration
- NCT04975308
In plain words
This large study tested a new oral drug called imlunestrant in women and men with hormone-sensitive advanced breast cancer whose disease had come back or progressed after earlier hormone treatment. In patients whose tumour had a mutation in the ESR1 gene, imlunestrant lengthened the time until the disease progressed compared with standard hormone treatment; but this advantage was not seen across all patients. Adding the drug abemaciclib to imlunestrant lengthened the time until progression further, but severe side effects were also more common with this combination. The choice of treatment should be made with the treating doctor, based on each patient's situation.
Key results
Treatment arms and regimens
Imlunestrant alone (331 patients).
Imlunestrant 400 mg orally once daily (days 1 to 28 of each 28-day cycle) until progression.
Standard endocrine therapy as a single agent (330 patients).
Endocrine therapy of the investigator's choice: exemestane 25 mg orally daily, or fulvestrant 500 mg intramuscularly on days 1 and 15 of cycle 1 and then day 1 of each 28-day cycle.
Combination of imlunestrant and abemaciclib (213 patients).
Imlunestrant 400 mg orally once daily + abemaciclib 150 mg orally twice daily, continuously in 28-day cycles.
Source of the regimen details: ClinicalTrials.gov NCT04975308
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Study population
Patients with oestrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer with recurrence or progression during or after treatment with an aromatase inhibitor. This prior treatment could have been given alone or with a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor.
Endpoints
The primary endpoints were investigator-assessed progression-free survival (PFS) in three comparisons: imlunestrant versus standard therapy in patients with ESR1 mutations; imlunestrant versus standard therapy in all patients; and imlunestrant + abemaciclib versus imlunestrant in all concurrently randomised patients.
Safety and side effects
Incidence of grade 3 or higher adverse events: 17.1% with imlunestrant, 20.7% with standard therapy and 48.6% with imlunestrant + abemaciclib.
Clinical significance and place in guidelines
According to the abstract, imlunestrant showed better PFS than standard endocrine therapy in patients with ESR1 mutations but was not significantly superior in the overall population. The combination of imlunestrant and abemaciclib improved PFS over imlunestrant alone regardless of ESR1 status, albeit with more grade 3 or higher adverse events. The abstract gives no information on drug approvals or the place of this regimen in guidelines; these should be checked in up-to-date sources. Overall survival data are not reported in the abstract.
Limitations
The trial was open-label and the primary endpoint (PFS) was investigator-assessed. The comparison of imlunestrant versus standard therapy in the overall population was not statistically significant. Overall survival results are not reported in the abstract. The exact type of standard therapy and the doses are not stated in the abstract and should be checked in the full text of the paper.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.