Imlunestrant Plus Verzenio: New Treatment Option for Certain Hormonal Therapy-Resistant Breast Cancers?
Imlunestrant, a new selective estrogen receptor downgrader (SERD), combined with Verzenio (chemical name: abemaciclib) seems to be a promising treatment option for some people diagnosed with advanced-stage, estrogen receptor-positive, HER2-negative breast cancer that grew while they were receiving hormonal therapy.
The results were presented at the 2024 San Antonio Breast Cancer Symposium and published simultaneously in The New England Journal of Medicine.
Key takeaways
Imlunestrant alone improved progression-free survival – how long people lived without the cancer growing – by about two months compared to Faslodex (chemical name: fulvestrant) or Aromasin (chemical name: exemestane) in people in the study with breast cancer with an ESR1 mutation.
Imlunestrant plus Verzenio improved progression-free survival by about four months in all the people in the study, whether or not the cancer had an ESR1 mutation.
The most common side effects among people who took imlunestrant, with or without Verzenio, were fatigue, diarrhea, nausea, anemia, and low white blood cell counts.
Imlunestrant is not yet approved by the U.S. Food and Drug Administration.
What the results mean for you
These results suggest that imlunestrant alone is effective against advanced-stage estrogen receptor-positive, HER2-negative breast cancers with an ESR1 mutation; combining imlunestrant with Verzenio was effective whether or not the cancer had an ESR1 mutation.
“Taken together, these data are encouraging for patients and show that imlunestrant, as monotherapy or combined with abemaciclib, could provide an all-oral targeted therapy option after progression on endocrine therapy for patients with ER-positive, HER2-negative advanced breast cancer,” said Komal Jhaveri, MD, the Patricia and James Cayne Chair for Junior Faculty at Memorial Sloan Kettering Cancer Center, who presented the results.
In 2023, Orserdu (chemical name: elascestrant), another oral SERD, was approved for people diagnosed with advanced-stage or metastatic, estrogen receptor-positive, HER2-negative breast cancer with an ESR1 mutation that grew after being treated with at least one hormonal therapy medicine. But Orserdu wasn’t studied in combination with Verzenio or another CDK4/6 inhibitor, so more studies are needed to know if that combination would help treat cancers without an ESR1 mutation.
Why do the study?
First treatments for advanced-stage hormone receptor-positive, HER2-negative breast cancer include an aromatase inhibitor and a CDK4/6 inhibitor, like Verzenio. But many cancers develop an ESR1 mutation, which means they stop responding to aromatase inhibitors. When this happens, doctors usually switch people to Faslodex, which is given as an injection.
Researchers have been working to create an alternative to Faslodex because it’s less effective against cancers with ESR1 mutations. Plus, the monthly injections into the buttocks are painful and inconvenient for many people.
About the study
The EMBER-3 study included 874 people diagnosed with advanced-stage estrogen receptor-positive, HER2-negative breast cancer that came back (recurred) or grew during or after treatment with an aromatase inhibitor, with or without a CDK4/6 inhibitor.
Nearly 99% of the people in the study were women. About 55% were white, 30% were Asian, and 3% were Black. A total of 256 people had breast cancer with an ESR1 mutation.
The researchers randomly assigned people to receive one of three treatment regimens:
331 people took imlunestrant alone
330 received Faslodex or took Aromasin (the standard of care); 88.5% received Faslodex
213 took imlunestrant and Verzenio
People were followed for about 1.5 years.
Detailed results
Among people with cancers with ESR1 mutations, progression-free survival was:
11.1 months for people taking imlunestrant and Verzenio
5.5 months for people taking imlunestrant
3.8 months for people receiving the standard of care
Among all the people in the study, progression-free survival was:
9.4 months for people taking imlunestrant and Verzenio
5.6 months for people taking imlunestrant
5.5 months for people receiving the standard of care
This means that in people with cancers with ESR1 mutations, imlunestrant reduced the risk of death or the cancer growing by 38%. Compared to imlunestrant alone, the combination of imlunestrant and Verzenio reduced the risk of death or the cancer growing by 43%.
Compared to people who received the standard of care, people who took imlunestrant were more likely to have fatigue (22.6% vs. 13.3%), diarrhea (21.4% vs. 11.7%), and nausea (17.1% vs. 13%). Still most of these side effects were grade 1, or mild.
Grade 3 or higher side effects happened in:
17.1% of people who took imlunestrant alone
20.7% of people who received the standard of care
48.6% of people who took imlunestrant and Verzenio
More than 86% of the people who took imlunestrant and Verzenio had diarrhea; most cases were grade 1 or 2.
Serious side effects occurred in:
10% of people who took imlunestrant
11.4% of people who received the standard of care
16.8% of people who took imlunestrant and Verzenio
Side effects led to stopping treatment in:
1% of people who received the standard of care
4% of people who took imlunestrant alone
6% of people who took imlunestrant and Verzenio
Jhaveri, K., et al. Imlunestrant, an Oral Selective Estrogen Receptor Degrader (SERD), as Monotherapy & Combined with Abemaciclib, for Patients with ER+, HER2-Advanced Breast Cancer (ABC), Pretreated with Endocrine Therapy (ET): Results of the Phase 3 EMBER-3 trial. 2024 San Antonio Breast Cancer Symposium. Abstract GS1-01
— Last updated on April 9, 2025 at 5:43 PM
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