Imlunestrant

Imlunestrant (Inluriyo) is a hormonal therapy pill approved by the Food and Drug Administration (FDA) to treat metastatic, estrogen receptor-positive, HER2-negative breast cancer that:

• Tests positive for an ESR1 mutation (a type of change in the genes that make estrogen receptors)
• Was previously treated with another type of hormonal therapy

Imlunestrant is part of a group of treatments called selective estrogen receptor degraders (SERDs). These medicines break down estrogen receptors on hormone receptor-positive breast cancer cells, stopping estrogen from helping the cancer grow.

Other FDA-approved SERDs are fulvestrant (Faslodex) and elacestrant (Orserdu).

How imlunestrant works

Imlunestrant works by attaching to estrogen receptors in hormone receptor-positive breast cancer cells. Once the medicine is attached to the receptors, it:

• Blocks estrogen from attaching to the estrogen receptors
• Breaks down the estrogen receptors so estrogen can no longer signal the cancer to grow and multiply

Imlunestrant treats metastatic breast cancers that have developed a mutation on the ESR1 gene. This gene controls the development of estrogen receptors.

In breast cancer that has an ESR1 mutation, the estrogen receptor behaves abnormally, like a switch that is always turned on and sending growth signals to the cancer cells. If an ESR1 mutation develops in the cancer cells, some hormonal therapies don’t work as well:

• Tamoxifen and fulvestrant are hormonal therapies that that work by attaching to estrogen receptors. In breast cancer with ESR1 mutations, these drugs can’t attach as well to the receptors.
• Aromatase inhibitors lower the amount of estrogen in the body, but they are not able to stop the estrogen receptors from signaling these cancer cells to grow.
• This can lead to breast cancer becoming resistant to these medicines and growing despite treatment.

Imlunestrant and other SERDs, such as elacestrant, are effective in treating metastatic breast cancer that has developed an ESR1 mutation. This is because these drugs break down the estrogen receptors and stop the cancer cells from receiving growth signals.

Who gets imlunestrant

Imlunestrant is approved by the FDA to treat certain breast cancers. To be eligible for treatment with imlunestrant, the cancer must:

• Be estrogen receptor-positive
• Be HER2-negative
• Be unresectable (locally advanced cancer that cannot be completely removed by surgery) or metastatic (the cancer has spread to other parts of the body)
• Test positive for a mutation on the ESR1 gene
• Have progressed while being treated with a different hormonal therapy

Researchers are also studying how well imlunestrant may work in combination with other medicines.

Testing for ESR1 mutations

When cancer stops responding to hormonal therapy, it can sometimes mean the cancer has developed a mutation in the ESR1 gene. This mutation can cause estrogen receptors to continue signaling cancer cells to grow even if you are taking certain hormonal therapy medicines, such as tamoxifen, fulvestrant, or aromatase inhibitors.

SERDs such as imlunestrant and elacestrant are able to attach to estrogen receptors in breast cancers that test positive for an ESR1 mutation. They can also break down the receptors. This means they may be effective when other hormonal therapies are no longer effective.

When the FDA approved imlunestrant, they also approved the Guardant 360 CDx blood test to detect ESR1 mutations. The test can confirm whether a person is eligible to take imlunestrant. Other tests can also be used to find ESR1 mutations. Learn more about ESR1 mutation testing.

Imlunestrant in pre- and perimenopausal women and men

Some people need to take a medicine called a gonadotropin-releasing hormone agonist, or GnRH agonist, while taking imlunestrant. They include:

• Pre- and perimenopausal women (women who are still getting regular menstrual periods)
• Men

GnRH agonists stop hormone production in different ways:

• In pre- and perimenopausal women, GnRH agonists are ovarian suppression drugs that stop the ovaries from producing estrogen.
• In men, fat cells can turn testosterone into estrogen. GnRH agonists stop the production of testosterone.

What the research shows

The 2025 FDA approval of imlunestrant for people with metastatic hormone receptor-positive breast cancer testing positive for an ESR1 mutation was based on results from a clinical trial called EMBER-3. The results were published Dec. 11, 2024, in the New England Journal of Medicine.

In the results, researchers compared outcomes for people who were given:

• Imlunestrant, or
• Standard treatment (a hormonal therapy—either an aromatase inhibitor or the SERD fulvestrant—chosen by the researchers)

Although people were randomly assigned to either imlunestrant or standard therapy, they knew what treatment they were getting. This is called an open-label trial.

People who participated in the study had advanced or metastatic breast cancer that was hormone receptor-positive and HER2-negative. The cancer had to have returned or grown while they were taking a hormonal therapy with an aromatase inhibitor.

Although the trial included people with and without ESR1 mutations detected in cancer cells, the approval was based on an analysis that was limited to just those with ESR1-mutated cancers.

The study found that:

• The people taking imlunestrant had a 38% lower risk of cancer growing and spreading (progressing) than those taking standard treatment.
• The people taking imlunestrant lived almost 2 months longer with no cancer progression than the people taking standard treatment.
• The most frequently reported side effects in people taking imlunestrant were fatigue, diarrhea, and nausea.

Researchers are continuing to study imlunestrant in different combinations and settings:

• The EMBER-3 trial is also studying imlunestrant in combination with abemaciclib (Verzenio) in metastatic breast cancer.
• The EMBER-4 trial is studying imlunestrant for treatment after surgery in early-stage breast cancer.

How imlunestrant is given

Imlunestrant is a pill you take by mouth. The standard dose is two pills taken once each day. Each pill is 200 milligrams.

Imlunestrant should be taken at the same time every day on an empty stomach. This means you should wait at least 1 hour after eating and you should not eat again for at least 2 hours after taking imlunestrant.

Take imlunestrant whole. The pill should not be split. It should not be crushed, chewed, or taken another way.

If you miss a dose by 6 hours or more, or you vomit after taking the pills, skip your dose for the day and take a regular dose the next day, as scheduled.

Imlunestrant is taken every day until the cancer progresses, or you decide with your doctor that the side effects are interfering with your daily life.

Side effects and things to remember

Most people in the EMBER-3 imlunestrant trial were able to keep taking imlunestrant without interruptions due to side effects. The most common side effects were fatigue, diarrhea, and nausea.

Researchers said that levels of these side effects were lower than those seen in other breast cancer treatments.

Common side effects include:

• Abdominal pain
• Anemia
• Back pain
• Decreased appetite
• Diarrhea
• Fatigue
• Joint pain
• Nausea
• Neutropenia
• Rash
• Vomiting

Your doctor may recommend regular blood tests to make sure your kidneys and liver are able to process imlunestrant without any problems.

Who should not take imlunestrant?

Imlunestrant shouldn’t be given to people who:

• Have liver problems
• Are pregnant, trying to become pregnant, or are the male partner of a woman trying to become pregnant
• Are breastfeeding; imlunestrant can pass into breast milk

Talk with your doctor about other concerns or questions you may have about using imlunestrant.

Paying for imlunestrant

If your care team has recommended imlunestrant for you and you are concerned about paying for treatment, there are things you can do:

• Contact your health insurance company to find out if imlunestrant is covered. Ask how long it may be covered and what the out-of-pocket cost will be for you.
• The makers of imlunestrant have a savings card program if you have additional costs not covered by insurance. The program is available to people who have private health insurance (non-Medicare and non-Medicaid). Learn more about the savings card and other support options:
  • Call the imlunestrant manufacturer, Lilly, at 1-800-545-5979 (1-800-LillyRx).
  • Visit the Lilly website for Inluriyo financial support.

You can learn about other available resources to help you pay for care and other expenses during breast cancer treatment on our Financial matters page.