Kisqali Plus Hormonal Therapy After Surgery for Early-Stage Breast Cancer Reduces Recurrence Risk
People who took the targeted therapy Kisqali (chemical name: ribociclib) plus an aromatase inhibitor after surgery to remove hormone receptor-positive, HER2-negative, early-stage breast cancer had better invasive disease-free survival than people who took only an aromatase inhibitor, according to results from the NATALEE trial.
The research was presented on June 2, 2023, at the American Society of Clinical Oncology (ASCO) Annual Meeting. Read the abstract of “Ribociclib and endocrine therapy as adjuvant treatment in patients with HR+/HER2- early breast cancer: Primary results from the phase III NATALEE trial.”
Listen to The Breastcancer.org Podcast episode featuring lead researcher Dennis Slamon, MD, discussing NATALEE results.
About Kisqali
Kisqali is a CDK4/6 inhibitor, a type of targeted therapy, used in combination with an aromatase inhibitor to treat advanced-stage, hormone receptor-positive, HER2-negative breast cancer that hasn’t been treated with hormonal therapy yet in pre-menopausal, peri-menopausal, and post-menopausal women.
Women who haven’t gone through menopause who take Kisqali also receive medicine to stop their ovaries from functioning.
Arimidex (chemical name: anastrozole), Aromasin (chemical name: exemestane), and Femara (chemical name: letrozole) are aromatase inhibitors.
Kisqali also is used in combination with the hormonal therapy Faslodex (chemical name: fulvestrant) to treat advanced-stage, hormone receptor-positive, HER2-negative breast cancer that hasn’t been treated with hormonal therapy yet, or has grown while being treated with a different hormonal therapy, in post-menopausal women.
Kisqali is a pill taken by mouth.
In the United States, Kisqali currently isn’t approved to treat early-stage breast cancer. But because it affects how certain types of breast cancer cells divide, researchers thought it could work against early-stage disease.
About the NATALEE trial
People diagnosed with early-stage, hormone receptor-positive, HER2-negative breast cancer usually take some type of hormonal therapy after surgery to reduce the risk of the cancer coming back (recurrence). Doctors call treatments given after surgery adjuvant treatments.
The NATALEE trial included 5,101 women and men diagnosed with early-stage, hormone receptor-positive, HER2-negative breast cancer. After breast cancer surgery, the researchers randomly assigned the people to one of two treatment groups:
2,549 people took Kisqali and an aromatase inhibitor (either Arimidex or Femara)
2,552 people took only an aromatase inhibitor
For three years, the people took Kisqali once a day for three weeks, and took one week off. The people took an aromatase inhibitor once a day for five or more years.
Researchers followed half the people for more than 34 months and half for between 21 and 34 months.
When the data were analyzed:
515 people (20.2%) had completed three years of Kisqali
1,449 people (56.8%) had completed two years of Kisqali
3,810 people (74.7%) were still taking medicine as part of the study
The results showed that adding Kisqali to an aromatase inhibitor reduced the risk of recurrence more and led to better invasive disease-free survival rates than Arimidex or Femara alone.
Disease-free survival rates are the percentage of people alive without cancer coming back after a specified period of time.
Three-year invasive disease-free survival rates were:
90.4% for people taking Kisqali and an aromatase inhibitor
87.1% for people taking only an aromatase inhibitor
This difference was statistically significant, which means that it was likely due to the difference in treatment and not just because of chance.
Better invasive disease-free survival was seen across all types of early-stage, hormone receptor-positive, HER2-negative breast cancer, including node-negative disease. No CDK4/6 inhibitors are approved to treat early-stage, node-negative disease.
Based on the results of the monarchE study, the U.S. Food and Drug Administration (FDA) approved the CDK4/6 inhibitor Verzenio (chemical name: abemaciclib) in combination with either tamoxifen or an aromatase inhibitor after surgery for this same type of breast cancer, but it must be node-positive disease.
Several researchers who commented on the results at the ASCO annual meeting, including Nadia Harbeck, MD, PhD, director of the breast center at LMU University Hospital in Munich, Germany, who is an internationally recognized medical oncologist, said the results are likely to change practice and give people and their doctors another CDK4/6 treatment option for early-stage, hormone receptor-positive, HER2-negative breast cancer.
Kisqali and Verzenio cause different side effects, so it’s likely to be the way people and their doctors decide which medicine is best for their unique situations.
Side effects
Both Kisqali and Verzenio can cause:
Kisqali is more likely to cause low white blood cell counts — called neutropenia by doctors — and Verzenio is more likely to cause more severe diarrhea.
Dr. Slamon told Breastcancer.org that the approved dose of Kisqali for metastatic breast cancer is 600 milligrams a day, while in the NATALEE study, people took 400 milligrams a day.
“Patients who were on the metastatic disease trial who had any side effect went on a dose reduction to 400 milligrams,” Dr. Slamon explained. “At the end of that metastatic disease trial, we were able to look at the outcomes for the patients that had a reduced dose, and it turns out their outcomes looked as good as the ones at the 600-milligram dose.”
So the researchers decided to use the lower dose for the NATALEE trial to see if they could reduce the rate of side effects, and they did.
“The other thing that’s taken into consideration is abemaciclib is approved for these high-risk patients, whereas ribociclib was tested in the lower-risk patients, not the lowest-risk but the lower-risk patients, the intermediate risk so to speak, and we found that we have a benefit there,” he added. “So, even in patients with stage II disease and node-negative disease, the drug appears to be having a benefit.”
What this means for you
If you’ve been diagnosed with early-stage, hormone receptor-positive, HER2-negative breast cancer, the current standard of care is surgery, and possibly chemotherapy, radiation, or both, followed by five to 10 years of hormonal therapy.
Still, even after completing hormonal therapy, more than 33% of people diagnosed with stage II or stage III disease have a recurrence, sometimes decades later.
If you’re deciding on treatments after surgery, the results of the NATALEE trial are likely to give you and your doctor another option to consider to reduce recurrence risk even more.
Although Kisqali is not currently approved for early-stage breast cancer, Novartis, the company that makes Kisqali, is expected to apply to the FDA for approval to use the medicine to treat early-stage disease.
After considering your unique situation, the side effects of each medicine, and your personal preferences, you can decide if Kisqali and an aromatase inhibitor after surgery is a good choice for you, once it is approved.
— Last updated on August 16, 2024 at 7:04 PM