The targeted therapy Kisqali (chemical name: ribociclib) is approved to be used in combination with an aromatase inhibitor to treat advanced-stage or metastatic hormone-receptor-positive, HER2-negative breast cancer that hasn’t been treated with hormonal therapy yet in postmenopausal women.
Kisqali is a cyclin-dependent 4/6 kinase inhibitor. A kinase is a type of protein in the body that helps control cell division. Ribociclib works by stopping cancer cells from dividing and growing. Kisqali is a pill taken by mouth.
Advanced-stage breast cancer is breast cancer that has spread to tissue near the breast, such as the chest wall. Metastatic breast cancer is cancer that has spread to parts of the body away from the breast, such as the bones or liver. Metastatic breast cancer is also considered advanced-stage disease.
An aromatase inhibitor is a type of hormonal therapy medicine used to treat hormone-receptor-positive breast cancer. There are three aromatase inhibitors:
- Arimidex (chemical name: anastrozole)
- Aromasin (chemical name: exemestane)
- Femara (chemical name: letrozole)
Because adding Kisqali to an aromatase inhibitor offered more benefits than the aromatase inhibitor alone in treating advanced-stage, hormone-receptor-positive, HER2-negative disease in postmenopausal women, researchers wondered if Kisqali could be a treatment option for premenopausal women diagnosed with the same type of breast cancer.
Results from MONALEESA-7 study suggest that Kisqali along with either an aromatase inhibitor or tamoxifen and goserelin, medicine to suppress ovarian function, offers better progression-free survival than just hormonal therapy and ovarian suppression.
The study was presented on Dec. 6, 2017 at the 2017 San Antonio Breast Cancer Symposium. Read the abstract of “First-line ribociclib vs placebo with goserelin and tamoxifen or a non-steroidal aromatase inhibitor in premenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer: Results from the randomized phase III MONALEESA-7 trial.”
Progression-free survival is how long the women lived before the cancer grew.
“A significant number of patients with metastatic breast cancer are, in fact, premenopausal, and that number may be slightly going up over time,” said Dr. Debu Tripathy, professor of medicine and chair of the Department of Breast Medical Oncology at the University of Texas MD Anderson Cancer Center, who presented the research. “In this country, it’s estimated that about 20% of patients are premenopausal and in other parts of the world it’s even more. This is the first trial that was actually dedicated to women who were premenopausal.
“We’ve known for many years that patients who are younger do have more aggressive breast cancer and the drugs that we use may work differently, so it was very important to design a study dedicated exclusively to this patient population so we could have the statistical power to make conclusive statements,” he continued. “In addition, tamoxifen, which is commonly used in premenopausal patients, has not been tested in combination with any of the CDK4/6 inhibitors like Kisqali or Ibrance. So, this was the first trial to compare those drugs as well in combination.”
The study included 672 premenopausal women diagnosed with advanced-stage hormone-receptor-positive, HER2-negative breast cancer. None of the women had been treated with hormonal therapy for the advanced-stage disease. Some of the women had received one course of chemotherapy for the advanced-stage disease while others had not been treated with chemotherapy.
The women were about 43 years old; 55% were white and about 30% were Asian.
The women were split into two treatment groups:
- 335 women were treated with Kisqali, either tamoxifen or an aromatase inhibitor, and goserelin to suppress ovarian function
- 337 women were treated with placebo (a dummy pill that looked just like Kisqali), either tamoxifen or an aromatase inhibitor, and goserelin
About 25% of the women in each treatment group were treated with tamoxifen while the rest were treated with an aromatase inhibitor.
The women continued to receive their assigned treatment as long as it was effective.
Progression-free survival was:
- 23.8 months for women treated with Kisqali
- 13.0 months for women treated with placebo
This difference was statistically significant, which means that it was likely due to the difference in treatment and not just because of chance.
“Progression-free survival was nearly doubled, and so that was a very favorable result,” said Tripathy. “There’s no difference in survival at this point, but very few patients, fortunately, have expired due to their disease. Longer follow-up is needed to determine whether the trial will meet its secondary endpoint of overall survival.”
Tripathy also said that progression-free survival with tamoxifen was similar to that with aromatase inhibitors. He said he was encouraged that both tamoxifen and aromatase inhibitor use had similar outcomes which would give patients an option if there were intolerable side effects with the aromatase inhibitors.
“[This is] also the first trial to show that ribociclib can be safely and effectively combined with either tamoxifen or a nonsteroidal aromatase inhibitor together with ovarian suppression using goserelin,” he explained. "Ribociclib combined with tamoxifen or a non-steroidal aromatase inhibitor plus goserelin is a potential new treatment option for premenopausal women with hormone-receptor-positive, HER2-negative advanced-stage breast cancer, regardless of disease-free interval or endocrine partner.”
Like almost all cancer treatments, Kisqali can cause side effects, some of them severe. The most common side effects seen in the MONALEESA-7 study were:
- low white blood cell counts (76% in the Kisqali arm vs. 8% in the placebo arm)
- hot flashes (34% in both arms)
- nausea (32% in the Kisqali arm vs. 20% in the placebo arm)
- joint pain (30% in the Kisqali arm vs. 27% in the placebo arm)
Four percent of the women in the Kisqali arm and 3% of women in the placebo arm stopped taking the medicines because of side effects.
“The side effect profile was pretty much in the same range,” Tripathy said. “A lot of the side effects were actually due to side effects we typically attribute to aromatase inhibitors, and about three-fourths of the patients were on aromatase inhibitors and one-quarter were on tamoxifen. That was actually up to the patient and physician, unless they had recently had one or the other drug in the early-stage setting. If it had been less than a year, then they had to go on the alternate drug. So a lot of the side effects were due to that. The one main side effect we saw due to Kisqali was a drop in the white cell count. It was usually asymptomatic. In fact, the development of an infection was quite rare; it was 2% or less.
“I would say that physicians and patients can feel more confident now that if they are premenopausal, that this is clearly an effective therapy,” he concluded.
If you’re a premenopausal woman who had been diagnosed with advanced-stage, hormone-receptor-positive, HER2-negative breast cancer and are deciding on hormonal therapy treatments, you may want to talk to your doctor about this study and ask if treatment with Kisqali makes sense for your unique situation.
For more information, visit the Breastcancer.org Kisqali pages.
Listen to a Breastcancer.org podcast with Dr. Tripathy about the MONALEESA-7 study.
Editor’s Note: On Jan. 3, 2018, Kisqali was granted breakthrough therapy designation by the U.S. Food and Drug Administration to be used in combination with tamoxifen or an aromatase inhibitor to treat advanced-stage or metastatic hormone-receptor-positive, HER2-negative breast cancer that hasn’t been treated with hormonal therapy before in premenopausal women.
On July 18, 2018, the FDA expanded the use of Kisqali. Kisqali is approved by the FDA to:
- be used in combination with an aromatase inhibitor to treat advanced-stage or metastatic, hormone-receptor-positive, HER2-negative breast cancer that hasn’t been treated with hormonal therapy yet in premenopausal, perimenopausal, and postmenopausal women; premenopausal and perimenopausal women treated with Kisqali also should be treated with a luteinizing hormone-releasing hormone agonist, such as Zoladex (chemical name: goserelin), to suppress ovarian function
- be used in combination with Faslodex (chemical name: fulvestrant) to treat advanced-stage or metastatic 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 postmenopausal women