Kisqali Plus Hormonal Therapy More Effective Than Chemotherapy as First Treatment for Advanced-Stage Breast Cancer
Pre-menopausal women diagnosed with advanced-stage, hormone receptor-positive, HER2-negative breast cancer who took Kisqali (chemical name: ribociclib) and hormonal therapy as a first treatment had better progression-free survival and fewer side effects than people who received chemotherapy, even if they also had visceral crisis, according to results from the RIGHT Choice trial.
The research, “Primary results from the randomized Phase II RIGHT Choice trial of premenopausal patients with aggressive HR+/HER2- advanced breast cancer treated with ribociclib + endocrine therapy vs physician’s choice combination chemotherapy,” was presented on Dec. 6, 2022 at the San Antonio Breast Cancer Symposium (SABCS).
Advanced-stage breast cancer is cancer that has spread to tissue near the breast. 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 considered advanced-stage disease.
When a person diagnosed with metastatic breast cancer has visceral crisis, it means the cancer has spread to a soft organ, such as the lungs or liver, and is threatening to shut down the organ.
Progression-free survival is how long a person lives without the cancer growing.
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.
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.
About the RIGHT Choice study
A CDK4/6 inhibitor plus hormonal therapy is commonly the first treatment for people diagnosed with advanced-stage, hormone receptor-positive, HER2-negative breast cancer. Still, some doctors recommend chemotherapy as the first treatment for this type of breast cancer if it has aggressive characteristics, such as visceral crisis.
The RIGHT Choice study included 222 pre- or peri-menopausal women diagnosed with advanced-stage, hormone receptor-positive, HER2-negative breast cancer with aggressive characteristics. None of the women had received systemic treatments for advanced-stage disease.
Systemic treatments are treatments that affect the whole body by going through the bloodstream. Chemotherapy medicines, hormonal therapy medicines, targeted therapy medicines, and immunotherapy medicines are examples of systemic treatments.
Of the women in the study:
about 76% were age 40 or younger
about 72% were diagnosed with de novo metastatic disease, which means metastatic breast cancer was the first diagnosis
more than 85% had liver or lung metastases
about 52% had visceral crisis
The researchers randomly split the women into two treatment groups:
112 women took Kisqali and either Arimidex or Femara, and also received Zoladex (chemical name: goserelin) to suppress ovarian function
110 women received the researchers’ choice of chemotherapy
The chemotherapy choices were:
Taxotere (chemical name: docetaxel) and Xeloda (chemical name: capecitabine)
Taxol (chemical name: paclitaxel) and Gemzar (chemical name: gemcitabine)
Xeloda and Navelbine (chemical name: vinorelbine)
The researchers followed half the women for more than two years and half for shorter periods of time. After analyzing the data, they found that:
45.5% of women were still taking Kisqali and hormonal therapy
23.6% of women were still receiving chemotherapy
About half the women in each treatment group stopped treatment because the cancer grew.
Progression-free survival was:
24 months for women taking Kisqali and hormonal therapy
12.3 months for women receiving chemotherapy
This difference was statistically significant, which means it was likely due to the difference in treatment and not just because of chance.
The Kisqali and hormonal therapy combination also worked about 10 months longer than chemotherapy. Time to treatment failure was:
18.6 months for women taking Kisqali and hormonal therapy
8.5 months for women receiving chemotherapy
Kisqali and hormonal therapy also caused fewer severe side effects than chemotherapy:
1.8% of women taking Kisqali and hormonal therapy had a serious side effect
8% of women receiving chemotherapy had a serious side effect
7.1% of women stopped taking Kisqali and hormonal therapy stopped because of side effects
23% of women stopped receiving chemotherapy because of side effects
The most common serious side effects in both treatment groups were:
low white blood cell counts
anemia (low red blood cell counts)
increased liver enzyme levels
“These findings suggest that, through the use of first-line ribociclib plus endocrine therapy, we may be able to avoid or delay chemotherapy and spare patients — even those with aggressive, life-threatening disease — the toxicities and discontinuations associated with chemotherapy,” Yen-Shen Lu, MD, PhD, professor at the National Taiwan University Hospital, said in a statement. Dr. Lu presented the research.
“Compared with combination chemotherapy, ribociclib plus endocrine therapy may offer more durable antitumor efficacy with better tolerability and compliance,” Dr. Lu continued. “Overall, these improvements in outcomes and tolerability should translate into an evolution of our standard of care for patients with hard-to-treat breast cancer, providing clinicians with guidance for treating this patient population.”
“These aren’t patients we’ve ever given CDK4/6 inhibitors to before,” Stephanie Graff, MD, told Breastcancer.org. “When we look at the CDK4/6 inhibitor trials, historically, we see high numbers of patients that are older, 65-plus. We see high patient numbers of bone-only metastatic disease. We see patients that often are completely asymptomatic from their metastatic breast cancer, eligible and enrolling [in] those trials, and this RIGHT Choice trial, just by the very presence of bulky, aggressive visceral disease, these are patients that are sick with their breast cancer.”
Dr. Graff is director of breast oncology at the Lifespan Cancer Institute at Brown University.
“And what we saw was that the CDK4/6 inhibitors worked,” Dr. Graff continued. “It improved. Their progression-free survival was much better with the CDK4/6 inhibitor than chemo; and although the chemotherapy patients responded a little bit faster, it wasn’t faster, dramatically. It was faster, like a few weeks. Not in a way that would have made a difference in that person’s long-term outcome, and the patients that got chemo didn’t feel as good. So, I think that this tells us that even in visceral disease, even in bulky disease, even in progressive disease, even in young disease, because the average age of patients in the RIGHT Choice was in their 40s, patients can do great on CDK4/6 inhibitors, and that’s really bolstering to see.”
What this means for you
If you’ve been diagnosed with advanced-stage, hormone receptor-positive, HER2-negative breast cancer and are deciding on first treatments for advanced-stage disease, you may want to ask your doctor about the RIGHT Choice study results and how they might apply to your unique situation.
Although the RIGHT Choice study was small, the results are promising. A number of doctors at the 2022 SABCS felt the results are practice-changing.
“It will change some of that standard of care,” Virginia Kaklamani, MD, said at a media briefing on the research. “We don’t use a lot of chemotherapy nowadays because of how well the CDK4/6 inhibitors work, but I think the little that we use is probably now dead.”
Dr. Kaklamani is professor of medicine in the Division of Hematology and Oncology at UT Health San Antonio.
Learn more about Kisqali.
— Last updated on May 26, 2023 at 4:58 PM