Adding abemaciclib to treatment leads to longer time without recurrence for high-risk, hormone receptor-positive early breast cancer

Update: Abemaciclib (Verzenio) was FDA approved for early-stage, high-risk breast cancer in October 2021. This article provides context about the FDA approval. 

The monarchE study found that adding the CDK 4/6 inhibitor abemacicilib (Verzenio) to hormonal therapy helped people with early-stage, hormone receptor-positive breast cancer who had a high risk of recurrence go longer without cancer returning.

The news was announced in a press release in mid-June by Eli Lilly and Company, the makers of abemaciclib. The full results will be presented at an upcoming conference.

This is the first study showing a CDK 4/6 inhibitor lessens the chance of recurrence for early-stage hormone receptor-positive, HER2-negative breast cancer. It’s an exciting development for people with high-risk early breast cancers, but questions remain about the best way to identify high-risk cancers and how to balance the benefits against the side effects and costs of up to 2 years of abemaciclib.

Background

CDK 4/6 inhibitors work by targeting certain proteins, cyclin-dependent kinases 4 and 6, that cause breast cancer cells to multiply. The Food and Drug Administration approved the first of these medicines, palbociclib (Ibrance), to treat metastatic, hormone receptor-positive, HER2-negative breast cancer in 2015. Abemaciclib and ribociclib (Kisqali) were approved soon after for similar uses. So far, all CDK 4/6 inhibitor approvals have been for metastatic breast cancer.

Abemacicilib has features that are different than other CDK 4/6 inhibitors, and may set it apart for some uses:

• It is the only CDK 4/6 inhibitor that is given continuously; the others require you to take regular breaks from the medicine.
• Abemaciclib is the only CDK 4/6 inhibitor FDA approved to be given alone, without a hormonal therapy.

Researchers are still learning about these differences and their importance in different treatment settings.

Since CDK 4/6 inhibitors became available, researchers have been interested in whether they could improve treatment for early-stage breast cancer. In a recent trial, adding palbociclib to treatment did not result in people going longer without breast cancer returning. The monarchE trial differed in two important ways: it only included people with high-risk breast cancers and it tested abemaciclib.

Design

The monarchE trial included 5,637 people with early-stage hormone receptor-positive, HER2-negative breast cancer. Everyone in the study was considered to have a breast cancer with high risk of returning based on at least one of these features:

• Cancer in four or more axillary lymph nodes.
• Cancer in one to three lymph nodes and had at least one other high-risk feature:
  • the tumor was 5 centimeters or larger
  • the tumor was grade 3
  • the centralized Ki-67 index was 20 percent or higher

Participants could be men or women of any menopausal status. They were randomized after getting surgery, and radiation therapy or chemotherapy if appropriate for the diagnosis. All participants were given at least 5 years of standard hormonal therapy with either tamoxifen or an aromatase inhibitor:

• The study group was given abemaciclib for up to 2 years with the hormonal therapy.
• The control group was given hormonal therapy alone.

The main interest for researchers was invasive disease-free survival, or how long people went without invasive breast cancer returning or a new diagnosis.

Results

Lilly announced that the monarchE trial met an early goal of improving invasive disease-free survival. The results show people given abemaciclib went longer without invasive breast cancer coming back than the group given hormonal therapy alone.

The specific results were not released and will not be known until the full study is provided, coming later this year. The announcement said the differences between the groups is statistically significant, meaning the benefit seen in this study of adding abemaciclib is likely not the result of chance.

“Data from the press release suggest that adding abemaciclib to adjuvant endocrine therapy has the potential to have a significant impact in our ability to reduce the risk of recurrence for our patients with high risk hormone-receptor positive breast cancer, and we eagerly await these highly anticipated data,” says Sara Tolaney, MD, MPH, a medical oncologist at Dana-Farber Cancer Institute in Boston.

The announcement does not share details about side effects but said they were in line with side effects reported in other studies of this medicine. Past studies show diarrhea was the most common side effect, reported by more than 80 percent of people taking the medicine. Neutropenia, low counts of certain blood cells, is also common, affecting between 37 and 46 percent of people in past studies.

Lilly says it plans to submit the data to regulators this year and also to present the study at an upcoming medical meeting.

What this means for you

These are the first results suggesting a CDK 4/6 inhibitor could prevent breast cancer from coming back after an early-stage, hormone receptor-positive breast cancer diagnosis. It’s exciting news for everyone waiting for new targeted therapies that have improved treatment for metastatic breast cancer to move into early-stage disease. But until the full report is released, it is uncertain how these findings would be used in practice.

The monarchE study involves adding a medicine to the standard schedule of treatments. Abemaciclib would not replace a piece of treatment, but would be given along with surgery and hormonal therapy, as well as chemotherapy and radiation if appropriate to your diagnosis. With the added treatment would come 2 years of added side effects and costs.

The full results will give regulators, your doctors, and you a better idea of what benefit abemaciclib will bring to early-stage breast cancer treatment. People who have been told that there is a low chance of breast cancer returning can be confident that they are getting treatment appropriate for your diagnosis. For those whose cancers have features that suggest a higher risk of recurrence, this news brings hope of another possible tool to reduce the risk of breast cancer coming back.