Fda Approves Lilly’s New Oral Combo Pill For Common Breast Cancer Mutation

• The FDA approved a new oral combo drug for a common breast cancer mutation on September 18.
• The treatment includes Inluriyo (imlunestrant) taken with Verzenio (abemaciclib) for adults with ER-positive, HER2-negative advanced or metastatic breast cancer with ESR1 mutation that has spread after hormone therapy.
• Results from a trial show that among 159 participants with ESR1 mutations, those taking the combination went a median of 11.1 months before their cancer spread, or they died, compared with 5.5 months for those taking Inluriyo alone.
• A blood test can show whether breast cancer has an ESR1 mutation, according to the FDA.

People with advanced breast cancer that has spread despite hormone therapy, and with tumors that carry a gene change called an ESR1 mutation, have a new treatment option. 

The Food and Drug Administration (FDA) approved the use of an all-oral combo pill on September 18: Inluriyo (imlunestrant) and Verzenio (abemaciclib), both manufactured by Eli Lilly and Company. 

Inluriyo blocks estrogen’s signal in certain breast cancer cells and helps break down the receptor that receives that signal, according to the drug’s FDA-approved prescribing information. Verzenio blocks two proteins, CDK4 and CDK6, that can help cancer cells grow and divide, according to its prescribing information.

Verzenio first won FDA approval in 2017, and Inluriyo was approved as a stand-alone treatment in September 2025.

The FDA approved Inluriyo and Verzenio for use together. Inluriyo shuts down the estrogen receptors that fuel the cancer, while Verzenio slows how fast cancer cells multiply.

Neil Iyengar, MD, a breast medical oncologist at Winship Cancer Institute of Emory University, told Healthline that, “the individual treatments are not necessarily new, but the combination is a new concept.”

Some cancer specialists already prescribed the combination, according to Komal Jhaveri, MD, a breast medical oncologist at Memorial Sloan Kettering Cancer Center in New York and lead researcher on the clinical trial that led to its approval.

“Now FDA has backed that with an official approval, so more patients can receive it without having any issues,” Jhaveri told Healthline.

Who is eligible for Inluriyo and Verzenio?

The combination is approved for adults whose breast cancer meets all of these conditions:

• The cancer is locally advanced, meaning it has grown into tissue or lymph nodes near the breast, or metastatic, meaning it has spread to distant parts of the body.
• The cancer is ER-positive, meaning estrogen helps drive its growth.
• The cancer is HER2-negative.
• An FDA-authorized test has confirmed an ESR1 mutation.
• The cancer grew after at least one round of hormone therapy, also called endocrine therapy.

What is an ESR1 mutation in breast cancer?

In ER-positive breast cancer, estrogen attaches to proteins called receptors, which can lead to cancer growth, according to the National Cancer Institute.

Hormone therapy either prevents estrogen from binding to those receptors or lowers estrogen levels, according to the American Cancer Society (ACS).

An ESR1 mutation changes the estrogen receptor in a way that “makes it stay turned on,” Hope Rugo, MD, chief of breast medical oncology at City of Hope in Los Angeles, told Healthline.

“And that mutation can develop while a person is receiving hormone therapy, and ultimately it makes the cancer able to resist the hormone therapy,” Iyengar said.

ESR1 mutations appear in about 1% of breast tumors at diagnosis but in 10% to 50% of metastatic cancers that have stopped responding to hormone therapy, according to the College of American Pathologists.

How the new drug combo differs from earlier treatments

People with metastatic ER-positive breast cancer usually start treatment with a hormone therapy paired with a CDK4/6 inhibitor, such as Verzenio, according to Iyengar.

The CDK4/6 inhibitor doesn’t work on its own, he said. When an ESR1 mutation makes the hormone therapy stop working, doctors can’t continue the CDK4/6 inhibitor by itself.

Until now, those patients typically switched to a newer hormone therapy pill, such as Inluriyo, alone, according to Iyengar.

The new approval allows patients to keep a targeted therapy as part of their treatment.

Pairing a hormone therapy with a targeted therapy helps overcome resistance and controls the cancer longer, according to Rugo.

“We don’t like giving single endocrine therapy all by itself anymore because we like to give patients combination therapy with targeted agents,” she said.

Pills instead of fulvestrant shots

Before the newer pills, the standard treatment after an ESR1 mutation was fulvestrant, a hormone therapy given as two shots per visit, according to Rugo.

Patients receive the shots every two weeks for the first three doses and then monthly, she said.

“But people hate the injection,” Rugo said. “Most patients will do better with the pill because they don’t have to have the injection.”

How effective is the Inluriyo-Verzenio combo?

The clinical trial that led to the approval, called EMBER-3, included 874 adults, according to the FDA.

Eli Lilly funded the clinical trial. The approval is based on results from a cohort of 159 participants with tumors that had ESR1 mutations.

In that group, those taking the combination went a median of 11.1 months before their cancer grew or they died, compared with 5.5 months for those taking Inluriyo alone, according to the FDA.

Tumors shrank in 35% of people taking the combination and in 15% of those taking Inluriyo alone, the FDA reported. The FDA noted that these results come from a closer look at part of the trial, not from its main research question.

When the FDA reviewed the results, it was too early to tell whether the combination helps people live longer, according to the agency.

“There isn’t any survival data from any of these trials. The trials weren’t powered to look at survival,” Rugo said.

Side effects of Inluriyo and Verzenio

In the EMBER-3 clinical trial, 86% of people taking both Verzenio and Inluriyo had diarrhea, and 9% had severe cases, according to Verzenio’s prescribing information.

Diarrhea is a known side effect of Verzenio, according to Jhaveri. Adding Inluriyo didn’t increase the incidence of diarrhea compared with pairing Verzenio with fulvestrant, she said.

About 6% of people taking the combination stopped treatment due to side effects, according to a 2026 analysis of EMBER-3 published in npj Breast Cancer.

People taking Verzenio should start anti-diarrhea medication, drink more fluids, and contact their care team at the first sign of loose stools, according to the prescribing information for the drug.

The FDA’s safety warnings for the combination also include:

• low white blood cell counts
• liver problems
• lung inflammation
• blood clots
• harm to a developing fetus during pregnancy

Doctors check blood counts and liver function before a patient starts Verzenio, then every 2 weeks for the first 2 months, monthly for the next 2 months, and as needed after that, according to the prescribing information.

Testing for an ESR1 mutation

A blood test that looks for tumor DNA can show whether breast cancer has an ESR1 mutation, according to the FDA. The FDA approved one such test, Guardant360 CDx, to identify people who may benefit from the combination.

“We would typically test for it when somebody was diagnosed with metastatic breast cancer, and then we would test for it again if their scans showed that the cancer was growing again,” Iyengar said.

Ask your doctor about Inluriyo and Verzenio

Verzenio and Inluriyo, plus an aromatase inhibitor, are currently listed as a first-line treatment option for hormone receptor-positive, HER2-negative metastatic breast cancer, according to the National Comprehensive Cancer Network (NCCN).

Breast cancer specialists are likely to be aware of the new two-drug combo, but those treated by general oncologists may need to bring it up with their healthcare professional, Rugo said.

Rugo suggested asking when it makes sense to check your blood for an ESR1 mutation, and whether the combination is a good option if your cancer is growing on your current treatment.

Questions to bring to your next oncology appointment

• Has my cancer been tested for an ESR1 mutation, and when should I be retested?
• Am I eligible for Inluriyo and Verzenio?
• I’ve taken a CDK4/6 inhibitor before. Is this combination still a good fit for me?
• How does this combination compare to my other treatment options?
• What’s our plan if I get diarrhea?

What’s next for ESR1-mutated breast cancer treatment?

The FDA granted accelerated approval to Etcamah (camizestrant), developed by AstraZeneca, on September 4.

Etcamah is for people whose ESR1 mutation shows up during their first treatment with an aromatase inhibitor, a type of hormone therapy, and a CDK4/6 inhibitor.

Doctors start Etcamah and keep the CDK4/6 inhibitor at the same dose the patient was taking when the ESR1 mutation showed up, according to the FDA’s approval notice.

The agency granted Etcamah accelerated approval based on how long patients went without their cancer worsening, measured from the point when the mutation first appeared in the blood, according to the FDA.

The FDA has required follow-up studies because it isn’t yet confirmed that switching treatment at that point, rather than when scans show the cancer is spreading, gives patients a meaningful benefit.

Patients in the clinical trial that led to the approval had blood tests every 2 to 3 months, according to Iyengar.

“So technically speaking, what the FDA has approved is two different strategies,” Iyengar said.

Early results show a short-term benefit from switching treatment based on blood tests rather than waiting for scans, but researchers are waiting for long-term results, he said.

Researchers are also studying whether Inluriyo helps people with early stage breast cancer. That study, EMBER-4, has enrolled more than 8,000 patients, and initial results are expected in 2027, according to Eli Lilly.

Rugo said patients should watch for more drug approvals over the next six months.

“I would just emphasize here that it’s a really exciting time because people are living longer after a diagnosis of breast cancer,” Iyengar said.