Positive topline results in trial for patients with early breast cancer

Novartis trialled its drug Kisqali plus endocrine therapy (ET) in a phase 3 trial, NATALEE, and found it met its primary endpoint at interim analysis demonstrating clinically meaningful benefit in a broad population of patients with EBC.

The Independent Data Monitoring Committee recommended stopping the trial early as the primary endpoint of invasive disease-free survival (iDFS) had been met. Kisqali plus ET significantly reduced the risk of disease recurrence, compared to standard adjuvant ET alone, with consistent benefit in patients with stage 2 and stage 3 EBC regardless of nodal involvement.

Dennis Slamon, trial lead investigator said: “While most patients are diagnosed and treated early with the aim to cure breast cancer, the risk of cancer returning, often as metastatic disease, peaks within three years after diagnosis, but never goes away completely.

“There is a critical need for new, well-tolerated options that keep patients cancer-free without disrupting quality of life. The NATALEE trial, where ribociclib was given for three years plus ET, was designed with these unmet needs in mind, and it is extremely encouraging that this study met its primary endpoint.”

NATALEE is the first and only positive phase 3 study of a CDK4/6 inhibitor demonstrating consistent benefit in a broad population of patients with stage 2 and 3 HR+/HR2- EBC at risk of recurrence, including those with no nodal involvement.

Approximately 30-60% of people with HR+/HER2- stage 2 and 3 EBC treated with ET only remain at risk of breast cancer recurrence.

Per the NATALEE study protocol, patient follow-up will continue to evaluate long-term outcomes, including overall survival.

"The positive topline results from NATALEE represent a major milestone in our ambition to expand the benefits of Kisqali to patients with earlier stages of breast cancer, building on the heritage of this effective treatment in HR+/HER2- metastatic breast cancer,” said Shreeram Aradhye, chief medical officer, at Novartis.

“These data have the potential to be paradigm-shifting for patients at risk of recurrence, including those with no nodal involvement, who have limited well-tolerated options to prevent recurrence. Our teams are working on submissions to health authorities around the world with the hope to bring Kisqali to many more patients diagnosed with breast cancer.”

Novartis said these findings build on the legacy of Kisqali in metastatic breast cancer (MBC), where it has consistently demonstrated overall survival benefit while preserving or improving quality of life across three phase 3 trials.

Updates to the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology for breast cancer, released in January 2023, recommend ribociclib (Kisqali) as the only Category 1 preferred CDK4/6 inhibitor for first-line treatment of patients with HR+/HER2- MBC when combined with an aromatase inhibitor (AI)15.