Updated results from a clinical trial show that a new treatment continues to be effective at stopping advanced breast cancer from progressing in some people with tumors that have grown resistant to standard therapy.
The new data also suggests that overall survival can be improved by giving the drug, imlunestrant (Inluriyo™), alone or in combination with a second drug, abemaciclib (Verzenio®), to patients with ER-positive, HER2-negative advanced breast cancer who had previously been treated with hormone therapy. More follow-up is needed to conclusively establish that this therapy extends patients’ lives.
Imlunestrant previously had been shown to improve progression-free survival (PFS) in this group of breast cancer patients. Progression-free survival is the time the cancer remains under control without getting worse.
“These results will change how many breast cancers are treated,” says Memorial Sloan Kettering Cancer Center (MSK) medical oncologist Komal Jhaveri, MD, FACP, FASCO, chair of the international study and its principal investigator at MSK. “With the latest data, people with ER-positive, HER2-negative advanced breast cancer with an ESR1 gene mutation had the longest progression-free survival we have ever seen — more than 11 months — if they received the imlunestrant plus abemaciclib combination.”
“In addition, while it’s too early to confirm that overall survival is improved,” Dr. Jhaveri says, “the new updated results are looking good and trending in the right direction.”
Dr. Jhaveri presented the latest results from the EMBER-3 clinical trial at the San Antonio Breast Cancer Symposium on December 12, 2025. Dr. Jhaveri was the lead and corresponding author of a paper simultaneously reporting the results in the Annals of Oncology.
Imlunestrant was approved by the U.S. Food and Drug Administration (FDA) as a single-drug treatment (monotherapy) in September 2025 for people with ER-positive, HER2-negative advanced breast cancer with an ESR1 gene mutation. That approval came after earlier results from EMBER-3 were reported in December 2024.
Imlunestrant Especially Effective When Combined With Abemaciclib
In addition to demonstrating the drug’s effectiveness when used alone, EMBER-3 showed that imlunestrant works especially well when combined with abemaciclib. The combination improved progression-free survival in patients with ER-positive, HER2-negative advanced breast cancer despite prior progression on CDK4/6 inhibitor therapy. CDK4/6 is an enzyme that is important for cell division.
Notably, the combined drugs were effective regardless of progression on a prior CDK4/6 inhibitor, whether or not there was a mutation in the ESR1 gene or in the PI3K pathway. PI3K is part of a signaling pathway that regulates cell growth. When PI3K is mutated, it can lead to uncontrolled growth and fuel cancer.
In the trial, the treatment — both imlunestrant alone and in combination with abemaciclib — did not cause significant side effects.
Updated Clinical Trial Results Show Sustained Benefit From Imlunestrant
The latest analysis from EMBER-3 provides more confirmation that the benefit from imlunestrant is lasting. EMBER-3 included 874 patients with ER-positive, HER2-negative advanced breast cancer whose disease had recurred or progressed during or after hormone therapy given alone or with a CDK4/6 inhibitor.
Participants were randomly assigned to receive either standard therapy, imlunestrant alone, or imlunestrant in combination with abemaciclib. At a median follow-up of 28.5 months:
- In patients with ESR1-mutated ER-positive, HER2-negative advanced breast cancer, median overall survival was nearly 50% longer for people receiving imlunestrant alone compared with people receiving standard therapy (34.5 months vs. 23.1 months).
- The big benefit came when the drugs were combined: For people in the combination therapy group, median progression-free survival was 10.9 months. For people in the imlunestrant-alone group, it was 5.5 months.
- Imlunestrant alone delayed the start of chemotherapy for patients with ESR1 mutations by 5.5 months. In the combination group, regardless of ESR1 mutation, the delay was 12.2 months.
“Delaying the start of chemotherapy is especially meaningful for patients with advanced breast cancer because chemotherapy often negatively affects quality of life,” Dr. Jhaveri says.
The benefit of the combination therapy was consistent across patient subgroups, including among patients who had received prior CDK4/6 therapy and regardless of PI3K pathway mutation status.
“The effectiveness of the combined therapy despite prior CDK4/6 inhibitors and regardless of ESR1 mutation or PI3K pathway mutation status is a major advance,” says Dr. Jhaveri. “Second-line therapies have traditionally been chosen partly based on whether the patient carried the mutations. Now there is potentially another treatment option without needing to test for these markers.”
In the short term, Eli Lilly and Company has submitted the updated EMBER-3 data to the FDA for review regarding approval of the imlunestrant and abemaciclib combination to treat patients with the ESR1 mutation.
Imlunestrant is taken as a pill, making ongoing treatment simple for patients. It also can penetrate the blood-brain barrier, offering the possibility that it could potentially treat breast cancer that has spread to the brain.
Dr. Jhaveri notes that MSK has been involved with the testing of imlunestrant from the beginning, collaborating with the manufacturer on the drug development plan.
Selective Estrogen Receptor Degraders (SERDs) Are a New Class of Cancer Treatments
What Are SERDs, and How Did MSK Help Develop Them?
Imlunestrant is part of a class of drugs called selective estrogen receptor degraders (SERDs). These drugs bind with estrogen receptors to stop estrogen from attaching to cancer cells and fueling their growth. They also degrade the receptor protein.
The SERD fulvestrant (Faslodex) was approved in 2002 and has been given to patients whose breast cancer became resistant to hormone therapy. But many tumors also begin to grow resistant to fulvestrant.
In 2013, MSK breast cancer specialist Sarat Chandarlapaty, MD, PhD, published important research showing how ESR1 gene mutations play a key role in resistance to hormone therapy — and to fulvestrant as well. This helped lay the groundwork for the next-generation SERDs.
The Latest Generation of SERDs Combat Fulvestrant Resistance
The newer SERDs, such as imlunestrant, are proving to be effective in people who develop resistance to fulvestrant. In 2023, the FDA approved the first of these next-generation SERDs, a drug called elacestrant (Orserdu™), for people whose tumors were ER-positive, HER2-negative, had continued to grow after hormone therapy, and had an ESR1 mutation.
Now imlunestrant offers an additional oral SERD therapy — and one that has especially lasting benefit when given in combination with abemaciclib. This includes patients who may not have an ESR1 or PI3K mutation.
“Imlunestrant offers advantages over fulvestrant,” Dr. Jhaveri says. “Fulvestrant is given by intramuscular injection in the clinic, which many patients find painful and burdensome. Being able to take imlunestrant as a pill makes life much easier for those being treated.”
