NATALEE Trial Supports Use of Kisqali with HR+/HER2- Early-Stage Breast Cancer at Increased Risk of Recurrence

“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. 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,” Dr. Yardley added.

Kisqali is a selective cyclin-dependent kinase inhibitor. It helps slow the progression of cancer by inhibiting two proteins: cyclin-dependent kinase 4 and 6 (CDK4/6).

These proteins, when over-activated, can enable cancer cells to grow and divide too quickly.

The data

The NATALEE phase III clinical trial was a randomized phase III trial that included more than 5,000 patients across 20 countries who were recruited between January 2019 and April 2021.

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
• 2,552 patients received only endocrine therapy after surgery

The latest analysis demonstrated that Kisqali plus endocrine therapy (ET), compared to ET alone, showed an improvement in rates of invasive disease-free survival (iDFS), distant recurrence-free survival (DRFS), and distant disease-free survival (DDFS) in high-risk EBC patients with N0 disease.

The addition of Kisqali to ET demonstrated a 28% risk reduction in iDFS in subgroup of patients with node-negative disease at high risk of recurrence (HR=0.72; 95% CI: 0.41, 1.27).

“Currently available targeted therapies are approved only for a small proportion of patients, leaving a large number of people diagnosed with HR+/HER2- early breast cancer at risk of cancer returning, particularly those with high-risk N0 tumors,” Jeff Legos, Executive Vice President, Global Head of Oncology Development, Novartis, said in a press release on the study.

“Our robust body of data continues to support the potential for Kisqali to benefit many more patients as they seek to reduce the likelihood of their cancer coming back with the addition of a CDK4/6 inhibitor to their endocrine treatment.”

Kisqali’s safety profile

Kisqali was associated with some side effects that could potentially be serious.

These included:

• Lung issues (trouble breathing, cough, chest pain)
• Skin reactions (rash, reddened skin, pain/burning, blistering of eyes, mouth)
• Heart rhythm problems (QT prolongation)
• Liver issues (hepatobiliary toxicity)
• Low white blood cells counts (neutropenia)

According to the drugmaker, some of the most common side effects associated with the drug were:

• Decreased white/red blood cell counts
• Nausea
• Tiredness
• Diarrhea
• Vomiting
• Headache
• Low blood sugar levels

In a conversation with SurvivorNet, Dr. Eleonora Teplinsky, head of Breast Medical Oncology at Valley Health System, explained how important it is for doctors to work with patients to understand if the benefits associated with the drug are worth the side effect risks.

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,” Dr. Teplinsky explained.

“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.

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