The U.S. Food and Drug Administration (FDA) has approved a new combination treatment for certain adults with advanced or metastatic breast cancer: imlunestrant (Inluriyo) used with abemaciclib (Verzenio).
The combination is approved for adults whose breast cancer is:
- Estrogen receptor (ER)-positive
- HER2-negative
- Locally advanced or metastatic
- ESR1-mutated, as identified with an FDA-authorized test
- Progressing after at least one line of endocrine therapy
This approval expands treatment options for people whose hormone receptor-positive breast cancer has developed resistance to prior endocrine therapy.
What is the new treatment?
Inluriyo is an oral estrogen receptor antagonist. It works by blocking and degrading estrogen receptors, which can help slow or stop the growth of breast cancers that rely on estrogen signaling.
Verzenio is a CDK4/6 inhibitor. It interferes with proteins that help cancer cells divide and multiply.
Using the medicines together targets two important drivers of ER-positive breast cancer: estrogen-receptor signaling and cancer-cell proliferation.
Who may be eligible?
The FDA approval applies to adults with ER-positive, HER2-negative advanced or metastatic breast cancer whose tumors have an ESR1 mutation and whose disease has progressed after at least one endocrine treatment.
ESR1 mutations can emerge over time, particularly after treatment with endocrine therapies such as aromatase inhibitors. These mutations may allow cancer cells to continue growing even when estrogen levels are reduced or blocked by earlier hormonal therapies.
Patients must have an ESR1 mutation identified by an FDA-authorized test. The FDA also approved the Guardant360 CDx blood-based test as a companion diagnostic to help identify people who may be candidates for treatment with Inluriyo plus Verzenio. The test looks for tumor DNA circulating in the bloodstream, often called circulating tumor DNA or ctDNA.
Results from the EMBER-3 trial
The approval was based on the phase 3 EMBER-3 clinical trial, which enrolled 874 adults with ER-positive, HER2-negative locally advanced or metastatic breast cancer. Participants had previously received an aromatase inhibitor alone or in combination with a CDK4/6 inhibitor.
Among the 159 patients whose tumors had an ESR1 mutation, the combination of Inluriyo plus Verzenio delayed cancer progression compared with Inluriyo alone:
| Outcome | Inluriyo + Verzenio | Inluriyo alone |
|---|---|---|
| Median progression-free survival | 11.1 months | 5.5 months |
| Risk of progression or death | 47% lower with the combination | — |
| Objective response rate | 35% | 15% |
Progression-free survival is the length of time patients live without their cancer growing or spreading. In the ESR1-mutated subgroup, the combination reduced the risk of disease progression or death by about 47% compared with imlunestrant alone, with a hazard ratio of 0.53. Overall-survival results were not yet mature at the time of the FDA’s analysis.
How is it taken?
The FDA-recommended dose is:
- Inluriyo: 400 mg by mouth once daily, taken on an empty stomach—at least two hours before food or one hour after food.
- Verzenio: 150 mg by mouth twice daily, with or without food.
Treatment is generally continued until the cancer progresses or side effects become unacceptable. Patients should follow their oncology team’s specific dosing and monitoring instructions.
Side effects and monitoring
Inluriyo’s prescribing information includes a warning about embryo-fetal toxicity, meaning it may cause harm to an unborn baby. Patients who could become pregnant should discuss contraception and pregnancy planning with their care team.
Verzenio has important warnings and precautions, including:
- Diarrhea
- Neutropenia, or low levels of infection-fighting white blood cells
- Interstitial lung disease or pneumonitis
- Liver problems
- Blood clots, also called venous thromboembolism
- Embryo-fetal toxicity
Because the combination includes Verzenio, oncology teams may monitor blood counts, liver function, symptoms of infection, diarrhea, breathing changes, and possible signs of a blood clot.
Why this matters
For people with ER-positive, HER2-negative metastatic breast cancer, molecular testing is increasingly important because treatment decisions may depend on changes that develop as the cancer evolves.
The new approval gives patients with an ESR1 mutation a chemotherapy-free, all-oral targeted treatment option following progression on endocrine therapy. It also reinforces the value of testing for ESR1 mutations using an FDA-authorized assay, including blood-based ctDNA testing when appropriate.
Questions to ask your doctor
If you have ER-positive, HER2-negative advanced or metastatic breast cancer, consider asking your oncology team:
- Has my cancer been tested for an ESR1 mutation?
- Could a blood-based ctDNA test help identify treatment options for me?
- Am I eligible for Inluriyo plus Verzenio?
- Have I previously received treatments that affect whether this combination is appropriate?
- What side effects should I watch for, and how will they be monitored?
Your oncology team can help determine whether this newly approved combination fits your treatment history, biomarker results, overall health, and personal treatment goals.
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