Adding Verzenio (chemical name: abemaciclib) to hormonal therapy after surgery to remove early-stage hormone-receptor-positive, HER2-negative breast cancer with a high risk of recurrence lowers that recurrence risk by about 25%, according to early results from the monarchE study.
The research was presented on Sept. 20, 2020, at the European Society for Medical Oncology (ESMO) Virtual Congress 2020 and published on the same day by the Journal of Clinical Oncology:
- Read the ESMO 2020 abstract of “Abemaciclib in high risk early breast cancer.”
- Read the Journal of Clinical Oncology article, “Abemaciclib Combined With Endocrine Therapy for the Adjuvant Treatment of HR+, HER2-, Node-Positive, High-Risk, Early Breast Cancer (monarchE).”
Listen to a podcast episode with lead researcher Stephen Johnston, M.D., professor of breast cancer medicine and consultant medical oncologist at The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research in London, about the monarchE study.
Doctors call treatments given after breast cancer surgery adjuvant treatments.
Verzenio is a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor. A kinase is a type of protein in the body that helps control cell division. Verzenio works by stopping cancer cells from dividing and growing. Verzenio is a pill taken by mouth.
Verzenio is used in combination with an aromatase inhibitor as the first hormonal therapy to treat advanced-stage or metastatic hormone-receptor-positive, HER2-negative breast cancer in postmenopausal women. Arimidex (chemical name: anastrozole), Aromasin (chemical name: exemestane), and Femara (chemical name: letrozole) are aromatase inhibitors.
Verzenio also is used in combination with Faslodex (chemical name: fulvestrant) to treat women diagnosed with hormone-receptor-positive, HER2-negative metastatic or advanced-stage breast cancer if the cancer grew after hormonal therapy treatment.
Verzenio is used alone to treat women and men diagnosed with hormone-receptor-positive, HER2-negative metastatic or advanced-stage breast cancer if the cancer grew after hormonal therapy treatment and earlier chemotherapy for metastatic disease.
Currently, Verzenio is not approved to treat early-stage breast cancer. But because earlier studies showed that Verzenio could help treat metastatic hormone-receptor-positive breast cancers that had become resistant to hormonal therapy, the researchers thought it might help reduce the risk of recurrence of certain early-stage breast cancers.
Cancer characteristics that lead to high recurrence risk
According to Johnston, up to 20% of people diagnosed with early-stage hormone-receptor-positive, HER2-negative breast cancer have the cancer come back within the first 10 years after treatment. In many cases, the cancer comes back in a part of the body away from the breast, such as the bones or liver. This is called distant or metastatic recurrence.
“We designed this trial really targeting those patients that we know still have up to a 20% risk of their cancer coming back within the first 5 years, despite everything that we give them in terms of the standard surgery, radiotherapy, and chemotherapy,” he told Breastcancer.org.
The characteristics of early-stage hormone-receptor-positive, HER2-negative breast cancer that give it a high risk of recurrence are:
- the cancer is found in four or more lymph nodes
- the cancer is 5 cm or larger in size
- the cancer is grade 3, which means the cells look very different from normal cells and are growing quickly in disorganized, irregular patterns
- the cancer has high levels of Ki-67, a protein in cells that increases as they prepare to divide into new cells; high Ki-67 levels mean the cancer cells are dividing and forming new cells very quickly
About the monarchE study
The monarchE study included 5,637 people diagnosed with early-stage hormone-receptor-positive, HER2-negative breast cancer with a high risk of recurrence — 5,601 women and 36 men. The people were from 38 countries around the world and joined the study between July 2017 and August 2019.
Most of the women in the study (56.5%) were postmenopausal when they were diagnosed. Nearly 60% of the people in the study were diagnosed with breast cancer that was in four or more lymph nodes.
As far as treatments other than hormonal therapy for the early-stage disease:
- 95.4% were treated with radiation therapy
- 95.4% were treated with chemotherapy
After breast cancer surgery, the people were randomly assigned to receive either:
- Verzenio plus hormonal therapy for 2 years
- hormonal therapy alone for 2 years
The hormonal therapy used was an aromatase inhibitor in 68.3% of the people and tamoxifen in 31.4%.
So far, the people have been followed for up to 2 years. At the time the data were analyzed, 12.5% of the people in the study had completed the full 2 years of treatment and 72.8% were still in the 2-year treatment period.
- 136 people treated with Verzenio and hormonal therapy had a recurrence
- 187 people treated with hormonal therapy alone had a recurrence
This difference was statistically significant, which means that it was likely due to the difference in treatment and not just because of chance.
When the researchers looked specifically at distant/metastatic recurrence, they found:
- 106 people treated with Verzenio and hormonal therapy had a distant recurrence
- 152 people treated with hormonal therapy alone had a distant recurrence
This difference also was statistically significant.
“There was a 25% reduction in the risk of invasive disease developing,” Johnston said. “If we looked just at what we call distant relapse-free survival — whether the cancer had gone to a second site such as the bone, liver, or whatever — there was a 28% reduction in risk. And this was really at the point of 2 years where we saw this difference developing. And the biggest reduction was in the risk of bone and liver metastases, which again, was what we suspected might happen, that we would have an impact on preventing metastatic sites of disease developing in an early time frame.
“This is the first time in more than 20 years that we have seen an advance in the adjuvant treatment of this form of breast cancer,” Johnston added.
“This is the first study to show that adding a CDK4/6 inhibitor to endocrine therapy significantly improves invasive disease-free survival in the adjuvant setting,” Giuseppe Curigliano, associate professor of medical oncology at the University of Milan, Italy, and chair of the ESMO Guidelines Committee, said in a statement. “This is a very important trial, and the findings will change practice. Once approved for high-risk hormone-receptor-positive, HER2-negative early breast cancer, the new standard of care for these patients will be to add 2 years of abemaciclib to endocrine therapy,” he suggested.
Verzenio side effects
Like almost all cancer medicines, Verzenio can cause side effects, some of them severe. Overall, 463 people (16.6%) treated with Verzenio and hormonal therapy and 21 people (0.8%) treated with hormonal therapy alone stopped treatment because of side effects.
The most common side effects experienced by people treated with Verzenio and hormonal therapy were:
- low white blood cell counts
“We know already from using abemaciclib in advanced disease, that diarrhea is the most common side effect, and we saw no new safety signals in the trial,” Johnston explained. “So, diarrhea was the most frequent adverse event. In terms of the overall frequency, up to 80% get some form of diarrhea, but the vast majority is grade 1 or 2, so less than 7%, I think it was, had what we call grade 3 diarrhea, which is the most troublesome form.
“The key thing is education of both the oncologist and the patient to act quickly,” he continued. “The diarrhea comes within 8 days [of starting treatment], so it’s in the first week or so, and it lasts on average 5 to 6 days. So, it’s short-lived, and the key thing is to give antidiarrheal medication, loperamide, as soon as the first loose stool occurs. And then if necessary, omit the dose of abemaciclib for a few days until the symptoms settle and/or dose reduce.”
What this means for you
If you’ve been diagnosed with early-stage hormone-receptor-positive, HER2-negative breast cancer with a high risk of recurrence, the results from the monarchE study are extremely promising. Lilly Oncology, the company that makes Verzenio, is submitting an application to the U.S. Food and Drug Administration (FDA) and the European Regulatory Authority for approval for Verzenio to be used to treat this type of early-stage breast cancer.
Stay tuned to Breastcancer.org Research News for the latest information on new approvals for medicines to treat breast cancer.
Editor’s Note: On Oct. 12, 2021, the FDA approved Verzenio in combination with either tamoxifen or an aromatase inhibitor after surgery to treat early-stage hormone-receptor-positive HER2-negative node-positive breast cancer with a high risk of recurrence (the cancer coming back) and a Ki-67 score of 20% or higher. Node-positive means cancer cells have been found in one or more lymph nodes. Ki-67 is a protein in cells that increases as they prepare to divide into new cells. A staining process can measure the percentage of tumor cells that are positive for Ki-67. The more positive cells there are, the more quickly they are dividing and forming new cells.
Written by: Jamie DePolo, senior editor
Reviewed by: Brian Wojciechowski, M.D., medical adviser
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