Novartis Kisqali® Shows Sustained Five-Year Benefit in Broad Early Breast Cancer Population
Novartis today released results from the five-year analysis of the pivotal Phase III NATALEE trial, confirming the long-term efficacy of Kisqali® (ribociclib) in patients with high-risk stage II and III hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) early breast cancer (EBC).
The analysis, based on a median follow-up of 58.4 months, demonstrated that treatment with Kisqali plus endocrine therapy (ET) provided a sustained reduction in the risk of recurrence, even two years after the completion of a three-year treatment course.
The study revealed a 28.4% reduction in the risk of invasive disease recurrence or death (hazard ratio [HR] = 0.716; 95% confidence interval [CI] 0.618–0.829; nominal p-value <0.0001) in patients receiving Kisqali in combination with ET compared with ET alone. This represents the broadest population of patients studied to date, encompassing individuals with both stage II and stage III disease, including those with node-negative tumors.
Five-year invasive disease-free survival (iDFS) rates further highlighted the clinical impact of Kisqali, with 85.5% of patients in the Kisqali plus ET arm remaining disease-free at five years compared with 81.0% in the ET alone arm.
This translates to an absolute improvement of 4.5%, underscoring a meaningful long-term benefit for patients at high risk of recurrence. These late-breaking findings are slated for presentation at the upcoming European Society for Medical Oncology (ESMO) Congress 2025.
Dr. John Crown, Consultant Medical Oncologist at St. Vincent’s University Hospital, Dublin, and investigator for the NATALEE trial, emphasized the importance of these results for patients. “For the thousands of people diagnosed with early breast cancer each year, the fear of recurrence, often manifesting as incurable advanced disease, weighs heavily on patients and their families,” he said.
“These five-year data show that the benefit of ribociclib persists well beyond the completion of treatment, offering these at-risk patients a significantly greater chance of living breast cancer-free.”
The trial also demonstrated consistency of benefit across clinically relevant subgroups. As follow-up progressed, confidence intervals narrowed, reinforcing the robustness of the observed iDFS advantage. This pattern was observed across subgroups defined by disease stage and nodal status, confirming the wide applicability of Kisqali in the early breast cancer setting.
Dushen Chetty, Global Head of Oncology and Hematology Development at Novartis, Ad Interim, highlighted the transformative potential of Kisqali.
“These data reinforce the potential of Kisqali to significantly reduce the long-term risk of breast cancer recurrence, extending well beyond the three-year treatment period. This provides physicians and patients with greater confidence in long-term disease management,” Chetty said.
“Kisqali is redefining the standard of care in adjuvant therapy, including in patients with node-negative disease. The consistency of benefit observed across both advanced and early breast cancer settings, together with Kisqali’s established safety profile, underscores its position as the CDK4/6 inhibitor with the most comprehensive Phase III evidence base for improving patient outcomes.”
Encouraging trends were also observed in overall survival (OS). Compared with the previous final iDFS analysis, the hazard ratio for OS improved to 0.800 (95% CI: 0.637–1.003; one-sided nominal p-value 0.026), suggesting a 20% reduction in the risk of death for patients treated with Kisqali plus ET versus ET alone. The NATALEE trial will continue to follow patients to ensure sufficient data are collected to confirm long-term OS and other outcomes.
iDFS results across pre-specified subgroups further illustrated the treatment benefit:
| Subgroup | Hazard Ratio | 95% CI | Absolute Risk Reduction at 5 Years |
|---|---|---|---|
| Overall population | 0.716 | 0.618–0.829 | 4.5% |
| Stage II | 0.660 | 0.493–0.884 | 3.7% |
| Stage III | 0.730 | 0.615–0.865 | 5.6% |
| Node-negative (N0) | 0.606 | 0.372–0.986 | 5.7% |
| Node-positive (N1-3) | 0.737 | 0.631–0.860 | 4.4% |
Long-term safety data remain consistent with previous reports. With a median of around two years after completion of Kisqali therapy, no new safety signals were identified. Rates of secondary primary malignancies (SPMs) were low and comparable between treatment arms, reported at 2.7% for Kisqali plus ET and 3.0% for ET alone. Only one SPM leading to death occurred in each group.
Importantly, Kisqali remains the only CDK4/6 inhibitor to demonstrate statistically significant OS benefits across three randomized controlled trials in advanced breast cancer (MONALEESA-2, MONALEESA-3, and MONALEESA-7). This underscores the established efficacy of ribociclib across the full spectrum of HR+/HER2- breast cancer, from early-stage adjuvant treatment to advanced disease settings.
In summary, the five-year NATALEE results confirm that Kisqali plus ET provides a sustained reduction in the risk of recurrence and demonstrates a favorable safety profile in a broad population of patients with early breast cancer.
These findings offer reassurance to physicians and patients seeking long-term strategies to reduce the risk of disease relapse and highlight Kisqali’s role in shaping the future standard of care for HR+/HER2- early breast cancer.
