Novartis Kisqali® Shows Significant 28% Reduction In Early Breast Cancer Recurrence Risk In 5-Year NATALEE Study

Novartis has announced the results from the five-year analysis of the pivotal Phase III NATALEE trial evaluating Kisqali® (ribociclib) in patients with high-risk early breast cancer. The analysis demonstrated a sustained benefit at a median of two years after completing three years of treatment with Kisqali (median follow-up: 58.4 months). The study showed a 28.4% reduction in the risk of recurrence (HR=0.716; 95% CI: 0.618–0.829; nominal p<0.0001) in the broadest population of patients with high-risk stage II and III hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) early breast cancer treated with Kisqali plus endocrine therapy (ET) compared with ET alone.

The five-year invasive disease-free survival (iDFS) rates were 85.5% in the Kisqali plus ET group versus 81.0% in the ET alone group, reflecting a clinically meaningful 4.5% improvement. These late-breaking results are being presented at the European Society for Medical Oncology (ESMO) Congress 2025.

Dr. John Crown, Consultant Medical Oncologist at St. Vincent's University Hospital in Dublin and a NATALEE investigator, emphasized that the fear of recurrence weighs heavily on patients and families. He stated that these five-year results demonstrate that the benefit of ribociclib persists well beyond the completion of treatment, providing patients at risk with a greater chance of remaining breast cancer-free.

As follow-up continued, confidence intervals narrowed, a trend that was consistent across clinically relevant subgroups, reinforcing the robustness of the observed iDFS benefit.

Dushen Chetty, Global Head of Oncology and Hematology Development at Novartis, Ad Interim, stated that the data highlight Kisqali’s potential to significantly reduce long-term breast cancer recurrence risk, extending beyond the three-year treatment period. He noted that the consistency of benefit across both advanced and early breast cancer settings, along with Kisqali’s established safety profile, underscores its position as the CDK4/6 inhibitor with the most comprehensive Phase III evidence for improving patient outcomes.

Overall survival (OS) continues to show an encouraging trend, with the hazard ratio improving to 0.800 (95% CI: 0.637–1.003; one-sided nominal p=0.026) compared with the final iDFS analysis (OS HR=0.892; 95% CI: 0.661–1.203), indicating a 20% reduction in the risk of death versus ET alone. The NATALEE trial will continue follow-up to gather sufficient data on OS and other long-term endpoints.

With a median follow-up of approximately two years after treatment completion, long-term safety showed no new signals. Rates of secondary primary malignancies (SPMs) were 2.7% in the Kisqali plus ET group and 3.0% in the ET alone group, with one SPM-related death reported in each group. Kisqali remains the only CDK4/6 inhibitor to demonstrate statistically significant overall survival benefits across three randomized controlled trials in advanced breast cancer, including MONALEESA-2, MONALEESA-3, and MONALEESA-7.