Kisqali improves overall survival in high-risk early breast cancer – Novartis

Novartis announced results from the six-year follow-up analysis of the Phase III NATALEE trial, reporting positive, clinically meaningful overall survival (OS) data with Kisqali (ribociclib) plus endocrine therapy (ET) compared to ET alone.

The study was in the broadest early breast cancer (eBC) population of patients with stage II and III HR+/HER2- early breast cancer at high risk of recurrence, including those with high-risk node-negative (N0) disease and all node-positive patients. Kisqali plus ET reduced the risk of death by nearly 20% (19.1%) compared to ET alone (HR=0.809; 95% CI: 0.661-0.989), with consistent overall survival benefit observed across all key subgroups. These late-breaking results will be presented at the European Society for Medical Oncology (ESMO) Annual Meeting 2026.

Patients have been off Kisqali for a median of three years (38 months) and have passed the five-year protocol-specified ET duration. The invasive disease-free survival (iDFS) benefit increased from 4.1% at five years to 5.3% at six years, underscoring the long-term value of dual inhibition, with benefit observed years after treatment completion.

Fewer patients treated with Kisqali plus ET experienced metastatic recurrence compared to ET alone, and OS continued to increase over time, with the absolute difference increasing from 1.2% at five years to 2.1% at six years. Breast-cancer specific survival (BCSS) was supportive of OS benefit, showing a ~30% reduction in risk of breast cancer-specific deaths (HR=0.709; 95% CI: 0.559-0.890) compared to ET alone.

Six-year NATALEE results reinforce long-term clinical benefit
“The NATALEE six-year data clearly demonstrate a clinically meaningful improvement in overall survival with ribociclib plus endocrine therapy,” said Dennis J. Slamon, MD, Chief of the Division of Hematology/Oncology, UCLA Department of Medicine. “These findings have very important implications for patients as well as health care providers worldwide and further strengthen the role of ribociclib in treating patients with HR+/HER2- early breast cancer at high risk of recurrence.”

“The clinically meaningful overall survival benefit observed in NATALEE underscores Kisqali as a standard of care for eligible patients and its foundational role in early breast cancer treatment,” said Andrea Myers, Global Head, Oncology Development, Novartis, Ad Interim. “These findings demonstrate the value of combining CDK4/6i with endocrine therapy in the broadest population of patients at high risk of recurrence, including those with high-risk node-negative disease and all node-positive patients.”

With longer follow-up, the safety profile remained consistent with previous analyses, and no new safety signals were observed. Overall, rates of secondary primary malignancies (SPMs) were 3.0% with Kisqali plus ET and 3.3% with ET alone. SPMs leading to death were 0.2% in both the Kisqali plus ET and ET alone arms.

Building on established Kisqali overall survival evidence
Kisqali is the only CDK4/6 inhibitor to demonstrate statistically significant OS benefit across three randomized controlled trials (MONALEESA-2, MONALEESA-3, and MONALEESA-7) in metastatic breast cancer and clinically meaningful OS in the broadest early breast cancer population at high risk of recurrence, including node-negative and node-positive disease.

“For those diagnosed with early breast cancer who face a higher risk of recurrence, having meaningful long-term overall survival data is invaluable,” said Jean A. Sachs, Chief Executive Officer, Living Beyond Breast Cancer. “These new insights help with important, shared decision-making conversations with their medical team, and make clear the importance of continued research to support those navigating complex decisions.”

About NATALEE
NATALEE is a global Phase III, multi-center, randomized, open-label trial to evaluate the efficacy and safety of Kisqali with ET as an adjuvant treatment versus ET alone in the broadest range of patients with stage II and III HR+/HER2- eBC, being conducted in collaboration with TRIO. The adjuvant ET in both treatment arms was a non-steroidal aromatase inhibitor (NSAI; anastrozole or letrozole) and goserelin, if applicable. The primary endpoint of NATALEE is invasive disease-free survival (iDFS) as defined by the Standardized Definitions for Efficacy End Points (STEEP) criteria. A total of 5,101 adult patients with HR+/HER2- eBC across 20 countries were randomized in the trial.