Novartis' Kisqali Is Now FDA Approved
- The Food and Drug Administration (FDA) has just approved Novartis’ Kisqali (ribociclib) in combination with an aromatase inhibitor as treatment for people with HR+/HER2- stage II and III early breast cancer (EBC) at high risk of recurrence.
- Breast cancer specialists tell SurvivorNet it’s important for patients to sit down with their doctors and discuss the benefits and risks of a CDK4/6 inhibitor like Ribociclib. Determining which patients will benefit the most, and endure the side effects to prevent recurrence, is a major topic for breast cancer specialists.
- Kisqali is CDK4/6 drug, which inhibit cyclin-dependent kinases, proteins that play a role in control cancer cell proliferation. CDK4/6 inhibitors work to interrupt the growth of cancer cells.
- An aromatase inhibitor is a drug used to block the activity of the aromatase enzyme and, consequently, stop the body from producing the hormone estrogen.
- Data from a clinical trial called NATALEE found that patients with this specific type of breast cancer who received a CDK4/6 inhibitor called Ribociclib (sold under brand names Kisqali and Kryxana), plus endocrine therapy, had a 25% lower risk of recurrence or death. But the longer term, absolute benefit is still something of a hot topic for debate among numerous oncologists interviewed by SurvivorNet.
Swiss multinational pharmaceutical corporation Novartis announced the news on Sept. 17, 2024, explaining how the new drug combo has been approved for “hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) stage II and III early breast cancer (EBC) at high risk of recurrence, including those with node-negative (N0) disease.”
Read More“The NATALEE trial enrolled patients with high risk hormone receptor positive early stage breast cancer and randomized them to receive standard endocrine therapy with or without the CDK four six inhibitor ribociclib, which was given for a course of three years,” said Dr. Heather McArthur, the Clinical Director of Breast Cancer at UT Southwestern in Dallas, Texas in an interview with SurvivorNet. “The addition of ribociclib improved invasive disease-free survival.”
“The NATALEE study was a little bit unique from the steady MonarchE study interrogating abemaciclib in the adjuvant setting for two years, in that not only was the duration of the CDK four six inhibitor longer in the NATALEE study, so three years versus two years in MonarchE, it also enrolled, NATALEE also enrolled patients with node negative disease.”
It was discovered that Kisqali “significantly reduced the risk of recurrence by 25 percent vs. endocrine therapy (ET) alone,” additionally, “consistent benefit and a well-tolerated safety profile seen across all subgroups in pivotal Phase III NATALEE trial, including patients with node-negative disease,” the news release explains.
Kisqali is CDK4/6 drug, which inhibit cyclin-dependent kinases, proteins that play a role in control cancer cell proliferation.
An aromatase inhibitor is a drug used to block the activity of the aromatase enzyme and, consequently, stop the body from producing the hormone estrogen.
Hormone Therapies for Breast Cancer: Aromatase Inhibitor
Dennis J. Slamon, M.D., Director of Clinical/Translational Research, UCLA Jonsson Comprehensive Cancer Center and Chairman of the Board of Translational Research In Oncology (TRIO) and NATALEE trial lead investigator, said in a statement, “The FDA approval of Kisqali for this early breast cancer population, including those with N0 disease, is a pivotal moment in improving our approach to care.
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“Today’s approval allows us to offer treatment with a CDK4/6 inhibitor to a significantly broader group of people as a powerful tool that, combined with endocrine therapy, can help further minimize their risk of cancer returning.”
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- NATALEE Trial Supports Use of Kisqali with HR+/HER2- Early-Stage Breast Cancer at Increased Risk of Recurrence
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- Treatment for HER2-Positive Breast Cancer
- HER2-Positive Metastatic Breast Cancer Treatment Options Explained
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What is Kisqali and How Does It Work?
KISQALI is a prescription medicine that is used in treatment of adults with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer that has progressed or spread to other parts of the body, in combination with:
- an aromatase inhibitor as the first endocrine-based therapy; or
- fulvestrant as the first endocrine-based therapy or following disease progression on endocrine therapy in postmenopausal women or in men
The official website for the drug explains, “KISQALI is a targeted treatment for HR+ (ER+ and/or PR+), HER2- metastatic breast cancer that blocks, or interferes with, substances that play a key role in cancer cell growth and survival. KISQALI affects cancer cells, but can also affect healthy cells.
“By combining KISQALI and either a nonsteroidal aromatase inhibitor (NSAI) or fulvestrant, you’ll have 2 medicines working differently, but together, to help slow the growth and spread of your metastatic breast cancer.”
As for an aromatase inhibitor, it’s a drug used to block the activity of the aromatase enzyme and, consequently, stop the body from producing the hormone estrogen.
“The way it works is that it’s used only in women who are post-menopausal so their ovaries are shut down or asleep but there’s still a little bit of hormone made in the body by an enzyme called aromatase,” Dr. Erica Mayer, a medical oncologist and a clinical investigator in the Breast Oncology Center at Dana-Farber Cancer Institute, previously told SurvivorNet.
“The aromatase inhibitor shuts down that enzyme so it takes the hormone level in the body as close down to zero as we can.”
Hormone Therapies for Breast Cancer: Aromatase Inhibitor
Can CDK4/6 Inhibitors Help Prevent Breast Cancer Recurrence?
CDK4/6 inhibitors work to interrupt the growth of cancer cells. SurvivorNet sat down with Dr. Eleonora Teplinsky, Head of Breast Medical Oncology at Valley Health System, to discuss how a CDK4/6 inhibitor, Ribociclib (sold under brand names Kisqali and Kryxana), is being studied for women with this specific type of breast cancer.
Referencing data obtained from the NATALEE phase III clinical trial, Dr. Teplinsky explained how breast cancer patients who received Ribociclib along with endocrine therapy (the current recommended treatment) had a 25% lower risk in recurrence or death.
Prior to the study, “Ribociclib was already approved for metastatic hormone receptor-positive breast cancer, but this study was looking to see if it has benefits in reducing recurrence in earlier stage breast cancer,” she explained.
The study looked at something called disease-free survival, which means patients are alive without their cancer recurring.
“In the group that received Ribociclib and endocrine therapy … at three years their disease-free survival was 90.4% compared to 87.1% in the group that received endocrine therapy alone,” Dr. Teplinsky said. This translates to a 3.3% “absolute improvement.”
How Does the CDK4/6 Inhibitor Work?
CDK4/6 inhibitors assist in slowing down cancer growth in women with HR+, HER2- breast cancer. Generally speaking, CDK4/CDK6 inhibitors are targeted therapies that fight off proteins known as the cyclin-dependent kinases 4 and 6 (CDK4/CDK6).
These proteins control how fast cells divide and multiply, and for women with breast cancer, these proteins can cause cancer cells to grow uncontrollably. That’s how CDK4/CDK6 inhibitors can help they slow down or prevent the proteins from multiplying.
Dr. Teplinsky stressed that doctors and patients should work together and have a candid discussion about side effects to determine if using a CDK4/6 inhibitor like Ribociclib is worth it.
“This all depends on the disease characteristics. Let’s say someone is lymph node-negative and they have a tumor size of three centimeters. They, based on this study, would be eligible to receive Ribociclib,” she explained. “…How do we make that decision and how do we have that conversation in the office about the risks and the benefits?
“We know there’s a 25% lower risk of recurrence. That’s great, but we also have to balance some of the side effects.”
She continued, “I think it’s a really hard decision for someone whose risk is a little bit lower to begin with, compared to someone who has a higher risk of recurrence. And how you navigate that is really going to be an individual conversation between patient and doctor and balancing all of those side effects with the benefit.”
Understanding Risk vs. Benefits
Dr. Teplinsky explained that it’s important for patients to understand the difference between “relative risk and absolute risk.”
While there was a 25% lower chance of cancer coming back among the population that did take Ribociclib in the NATALEE trial, “that translates into a 3.3% absolute risk,” she explained. “When you look at the numbers, 87.1% of patients who did not recieve Ribociclib did not experience a recurrence compared to 90.4% of patients who did receive Ribociclib and did not experience a recurrence.”
She continued, “I think the challenge if you were a patient and trying to figure this out is, how do you know if you would fall into that 3.3%? And, and we don’t know.”
Dr. Teplinsky is prepared to speak with her patients about the new medication available for them as she sees the benefit in making her “patients partners in their healthcare and having them be their own health advocates.”
Common possible side effects of Ribociclib include:
- Neutropenia, which is a low count of a type of white blood cell called neutrophils, which helps fight certain infections
- Nausea
- Infections
- Fatigue
- Diarrhea
- Leukopenia, which is a low white blood cell count
- Vomiting
- Alopecia, a type of hair loss
- Headache
- Constipation
- Rash
- Cough
Dr. Teplinsky also notes that adverse effects include lung disease and elevated liver enzymes, which can indicate the liver is inflamed or damaged.
“I think it’s really important to say, ‘Look, we have this new medication, here are the benefits, here are the side effects,” Dr. Teplinsky added. “Then really work through each individual patient about whether it’s something that is going to be right for them.”
Contributing: SurvivorNet Staff
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