News > Abemaciclib, everolimus studied in high-risk, early-stage HR-positive breast cancer

Abemaciclib, everolimus studied in high-risk, early-stage HR-positive breast cancer

New findings from two studies presented at SABCS confirm abemaciclib plus endocrine therapy reduces risk of recurrence, while adding everolimus does not improve outcomes 


Benefit of abemaciclib increases over time

People who take abemaciclib (Verzenio) do better over time, according to new results from the monarchE randomized controlled trial presented on December 6 at SABCS and published online the same day in The Lancet. These findings confirm that abemaciclib plus endocrine therapy reduces risk of breast cancer recurrence more effectively than endocrine therapy alone.


Abemaciclib belongs to a newer class of drugs called CDK 4/6 inhibitors. These targeted therapies work against cancer by blocking the CDK 4 and 6 proteins from signaling cancer cells to grow and divide. Three drugs in this category are FDA approved to treat metastatic breast cancer.

In October 2021, the FDA approved abemaciclib with endocrine therapy for the treatment of early-stage, HR-positive, HER2-negative, and node-positive breast cancers that are at high risk for recurrence. High risk was defined in part by a Ki-67 score of greater than or equal to 20%. Doctors determine the Ki-67 score through laboratory testing; a higher score reflects faster cancer growth. The trial results that led to approval were statistically significant but included only 15.5 months of follow-up. The length of follow-up is especially important for hormone receptor-positive breast cancers, because they tend to recur after longer periods than other subtypes of breast cancer. This week’s news confirms the benefit of abemaciclib after a longer time.


Abemaciclib reduces recurrence and, in fact, its benefit becomes stronger over time. The study sample included 5,637 participants who were randomly assigned to receive abemaciclib plus endocrine therapy or endocrine therapy alone. Nearly all had previously had chemotherapy. At four years, people on abemaciclib had higher rates of invasive disease-free survival (IDFS) and distant relapse-free survival compared to those taking only endocrine therapy. There was a difference of 6.4% IDFS over four years, compared to 2.8% over two years and 4.8% over three years. At the time of this analysis, participants were no longer taking abemaciclib.

Of those who took abemaciclib, 125 people developed metastatic disease compared to 249 in the group that took endocrine therapy alone. It is too early to tell whether there will be an impact on overall survival.

The research team looked at subgroups based on number of lymph nodes, tumor grade, tumor size, adjuvant versus neoadjuvant chemotherapy, menopausal status, under or over age 65, tumor stage, and race. The results held up across all subgroups. Notably, the race analysis compared white to Asian to other, reflecting the dominance of those two racial groups in the trial, which included 64 American Indian or Alaska Natives (2.3%) and 57 Black participants (2%). The 33 participants of Hispanic origin represented 8.3% of the U.S. study population.

In terms of side effects, people who took abemaciclib were more likely to develop lower white blood cell counts in the form of neutropenia and leukopenia, increasing their vulnerability to infection. Nearly 20% of people in the abemaciclib group developed grade three or four neutropenia (or more severe neutropenia) compared to less than 1% of those who took only endocrine therapy. Diarrhea was also more common in the study group.

What these findings mean for you

These results confirm the benefit of abemaciclib plus endocrine therapy to treat early-stage, high-risk, HR-positive, HER2-negative breast cancer. This is good news for those who have taken or are taking this medicine.

The Ki-67 cutoff for participation in this study was 20%. If the cancer meets all criteria but has a slightly lower Ki-67 score, you may want to discuss these results with your doctor.

Given that most people with this type of early-stage disease respond well to treatment, there is not yet enough data to say whether there will be a benefit to overall survival. However, there were fewer deaths among the group taking abemaciclib.

In general, people taking abemaciclib tolerate it well but they do have more side effects than those taking endocrine therapy alone. Talk with your healthcare team about the side effects before starting this or any cancer therapy, as well as ways you can prevent or manage them.

Addition of everolimus shows no benefit over hormonal therapy alone

A year of everolimus (Afinitor) did not improve either invasive disease-free survival or overall survival for most people. That is the finding of an analysis of data from SWOG S1207, a phase III randomized, placebo-controlled clinical trial conducted by the Cancer Research Network (formerly the Southwest Oncology Group).


Everolimus is an mTOR inhibitor. The mTOR pathway can be resistant to endocrine therapy. Doctors hoped that adding everolimus to endocrine therapy would improve outcomes.

This medication is currently FDA approved for people with metastatic breast cancer, and the researchers sought to study whether it could have an impact on preventing recurrences in people with high risk early-stage disease.


SWOG S1207 included 1,939 people aged 18 and older with invasive HR-positive, HER2-negative breast cancer previously treated with chemotherapy. The participants had cancers considered high risk for recurrence or metastasis based on some combination of Oncotype DX testing results, MammaPrint high-risk category, tumor size or grade, the number of lymph nodes affected, or the presence of residual disease after treatment.

Participants took everolimus for one year along with endocrine therapy. People in the control group took a placebo, a non-active pill. Everolimus did not improve IDFS or overall survival.

The study dose of 10 mg was not well tolerated by many participants, with 35% experiencing a side effect of grade three or higher, or a very severe side effect. Common side effects include swelling or soreness in the mouth, changes in blood cell counts, fatigue, and heart side effects such as high blood pressure or hypertriglyceridemia. Many people taking everolimus did not complete the study because of the side effects of the drug.

There was one exception to the overall study results: premenopausal women had better IDFS on everolimus. The reason for this is not yet known and could relate to the number of people who chose to remain on therapy, the choice of endocrine therapy, or something else entirely. This finding may be the subject of future study.

What these findings mean for you

If you are taking everolimus for early-stage disease, talk with your doctor about these results. Everolimus was hard to tolerate for many people, so the results of this study may provide valuable information for people who are experiencing side effects of this drug.

While the study showed no benefit for postmenopausal women, the information for premenopausal women is less clear. There are many options to treat HR-positive early-stage breast cancer. Work with your healthcare team to weigh the pros and cons of each and develop a treatment plan that is right for you.


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