For Women With the Most Common Type of Breast Cancer, Exciting New Drug Called Kisqali May Cut the Risk of Cancer Returning After Treatment

“More than one in three patients diagnosed with early-stage breast cancer, regardless of nodal involvement [if cancer is also affecting lymph nodes], are at risk of experiencing recurrent disease despite treatment with standard chemotherapy and/or endocrine therapy,” explained Dr. Denise A. Yardley, a medical oncologist and principal investigator on the NATALEE trial, which studied the drug.

“Notably, the NATALEE trial has shed light on the node-negative patient population, an important at-risk subgroup that could benefit from more options to reduce their risk of their cancer returning.”

Dr. Yardley explained that the trial’s results suggest the drug, when combined with endocrine therapy, could significantly lower the risk of cancer returning for these patients.

“The findings from this trial underscore the efficacy of ribociclib in early-stage node-negative breast cancer, highlighting its role as a viable and well-tolerated treatment intervention that could significantly diminish the recurrence risk for this particular group.”

Data presented at ASCO’s 2024 annual meeting has shown evidence regarding the efficacy of Kisqali, which works to interrupt the growth of cancer cells in hormone receptor-positive (HR+) breast cancer.

When a tumor is “hormone receptor-positive,” it means that a pathologist has run special tests on the cancer to determine that it is positive for either the estrogen and/or progesterone receptor.

Hormone positive (HR+) and HER2 negative (HER2-) breast cancer is the most common type of breast cancer, accounting for about 70% of new cases worldwide per year.

How Does Kisqali Help Prevent Recurrence?

According to the new study, adding Kisqali improves outcomes: it reduced the risk of progression or death by about 25%. However, this may not be quite as significant as it seems for all patients.

SurvivorNet spoke to Dr. Eleonora Teplinsky, a board certified medical oncologist specialized in breast and gynecologic cancer at Valley Health System in New Jersey, to understand more about the research.

“What that translates into, is that about 93% of patients who received ribociclib and regular endocrine therapy were alive without recurrence or death compared to about 90% of patients who received regular endocrine therapy alone.”

“It’s all in the nuances and in the details. Because a lot of the big headlines are going to read new drug reduces risk of recurrence by 25%, right? And that’s true, it’s a relative risk reduction. But people seeing that are going to say, ‘wow, this is great.’

Dr. Eleonora Teplinsky breaks down the benefits of using Kisqali.

“Then you translate that into an absolute gain, only about 3% [will have] benefit. Meaning that out of a hundred women, three more will not experience disease recurrence or death or progression. I will have some patients that say to me, I will do everything to not experience a recurrence. So for me, that 3% is worth it. And other women will say, I appreciate that benefit, but I don’t want to risk the toxicity. Or they’ve tried it and they’ve experienced toxicity and they want to stop. And so that’s where it’s that individual shared decision making as well,” Dr. Teplinsky added.

What is Kisqali?

Ribociclib (Kisqali) belongs to a class of medications known as kinase inhibitors which block the actions of kinase, a type of protein in cells that play a key role in growth, metabolism, and cell repair. Inhibiting kinase in cancer cells slows down the cancer from growing and spreading.

Kisqali is usually taken once daily in pill form along with the NSAI hormone therapy.

Doctors determine what type of cancer a patient has before treatment with a test called a biopsy. This involves removing a small sample of the tumor for testing in the lab.

If a patient’s disease is metastatic, hormone receptor positive, HER2 negative, then the combination therapy can even be considered as a first-line treatment, meaning it is is the first treatment doctors will use.

How Does Kisqali Work?

Cancer cells divide and grow by repeatedly going through a series of proliferation events called the “cell cycle.” This cycle is highly complex and regulated, meaning that several proteins within the tumor cells must be activated in a specific way at specific times for the cells to proliferate. CDKs, including CDK4/6, are just such proteins. They control key events in the cell cycle pathway, which makes them great targets for anti-cancer drugs, such as CDK inhibitors — which is the class of drugs Kisqali belongs to.

Kisqali, however, cannot work alone. Cancer cells also have other proteins that control their growth. In response to CDKs being blocked, they can rev up the production of these other proteins to compensate for the CDK inhibition. This can effectively render CDK inhibitors useless. One way to counteract this is to inhibit such compensatory pathways as well. Thus, Kisqali can be paired with endocrine therapies, another class of drugs used to treat breast cancer.

Endocrine therapy blocks hormones, such as estrogen and progesterone. These hormones can interact with certain proteins — estrogen receptor (ER) and progesterone receptor (PR) — present on the surface of breast cancer cells and fuel their growth. Such cancers are termed hormone-receptor-positive (HR+) cancers. When these cancers are starved of hormones, they are not able to continue growing.

By pairing Kisqali and endocrine therapy, clinicians can launch a multi-pronged attack that cannot be easily compensated by breast cancer cells.

Dr. Elizabeth Comen explains how breast cancer is fueled by different receptors. 

What’s the Data?

The NATALEE phase III clinical trial was a randomized phase III trial that included more than 5,000 men and women recruited between January 2019 and April 2021.

A phase III trial offers the highest level of evidence for the benefit of a new treatment.

All patients included in the study had early-stage breast cancer, meaning they had a small tumor in the breast without spreading to other organs (stage IIA, stage IIB, or stage III, per AJCC)

All patients had HR+, HER2- breast cancer.

After surgery, patients were randomized into two groups: 2,549 patients received ribociclib and endocrine therapy after surgery, while 2,552 patients received only endocrine therapy after surgery.

The latest analysis shows that combining Kisqali with endocrine therapy improves outcomes for high-risk early breast cancer patients compared to using endocrine therapy alone. Specifically, it increases the chances of staying free from invasive disease, distant recurrence, and distant disease.

For patients with node-negative disease who are at high risk of cancer coming back, adding Kisqali to endocrine therapy reduces the risk of recurrence by 25 to 28%.

What are the Side Effects?

Dr. Teplinsky stresses that patients should understand some of the potential side effects of Kisqali, and discuss them with their doctors before treatment.

Possible side effects may include:

• Low white blood cell counts, such as neutropenia (which can cause fever, chills, cough and more)
• Nausea or vomiting
• Diarrhea
• Fatigue

“The side effects look different in every single person,” Dr. Teplinsky said. “So it’s sometimes hard to know how someone will tolerate the medication until we put them on it.”

She indicated that it’s important for patients to understand that they could be on Kisqali for years, which means they could experience a symptom like diarrhea for an extended period. Dr. Teplinsky said patients should take this into consideration with their doctor when deciding together if the drug’s benefits outweigh risks.

For example, the negative side effects may be outweighed by the benefit for a patient who has a high risk of the cancer returning.

However, “I think it’s a really hard decision for someone whose risk is a little bit lower to begin with,” she said.

“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,” Dr. Teplinsky said.

And if you do experience symptoms, talk with your doctor, because they can help you find ways to manage them and have a better quality of life while taking the drug.

Questions to Ask Your Doctor

It’s important for patients to know that if they have a higher chance of their early-stage HR+, HER2- breast cancer returning after surgery, there may be options available to prevent that from happening.

Here are some questions you may consider asking your doctor to help get the conversation started:

• Does my breast cancer have a higher chance of returning?
• Would a CDK4/6 inhibitor help prevent it from coming back?
• Am I eligible to receive Kisqali?
• How do I know my hormone receptor or HER2 status?
• How will I feel during treatment?
• What are the most common side effects of Kisqali?
• Are there ways to manage the side effects?

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