In an updated analysis of the Phase III NATALEE trial, Novartis' Kisqali (ribociclib) combined with endocrine therapy (ET) demonstrated a sustained reduction in the risk of recurrence for patients with stage II and III hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) early breast cancer (EBC). The study revealed a 28.5% reduction in recurrence risk (HR=0.715; 95% CI 0.609–0.840; P <0.0001) compared to ET alone, even after the three-year treatment period.
The data, presented at the European Society for Medical Oncology (ESMO) Congress 2024, highlight the continued invasive disease-free survival (iDFS) benefit across all pre-specified patient subgroups, including those with node-negative disease. This is particularly significant as patients with node-negative disease often have limited treatment options beyond endocrine therapy.
Consistent Efficacy Across Subgroups
The four-year iDFS rates showed notable improvements with the Kisqali + ET combination across various subgroups:
- Intention-To-Treat Population: 88.5% with Kisqali + ET vs. 83.6% with ET alone (HR=0.715; 95% CI 0.609–0.840)
- AJCC Tumor Stage II: 93.9% with Kisqali + ET vs. 89.6% with ET alone (HR=0.644; 95% CI 0.468–0.887)
- AJCC Tumor Stage III: 84.3% with Kisqali + ET vs. 78.4% with ET alone (HR=0.737; 95% CI 0.611–0.888)
- Node-negative disease: 92.1% with Kisqali + ET vs. 87.0% with ET alone (HR=0.666; 95% CI 0.397–1.118)
Secondary Endpoints and Safety
Consistent results were observed across secondary efficacy endpoints, including distant disease-free survival (HR=0.715; 95% CI 0.604–0.847; P <0.0001). There was also a trend for improvement in overall survival (HR=0.827; 95% CI 0.636–1.074; one-sided P value=0.0766), although further follow-up is planned to obtain more mature overall survival data.
The safety profile of Kisqali remained consistent with previously reported results. Adverse events (AEs) of special interest (grade 3 or higher) included neutropenia (44.4%), liver-related AEs (8.6%), and QT interval prolongation (1.0%).
Expert Commentary
"Clinicians are eager to address the substantial risk of cancer coming back as metastatic disease for patients diagnosed with HR+/HER2- early-stage breast cancer," said Peter A. Fasching, M.D., Professor of Translational Medicine, University Hospital Erlangen and Comprehensive Cancer Center Erlangen-EMN and NATALEE trial investigator. "With longer follow-up, the clinically relevant benefit of adding ribociclib to endocrine therapy continues to improve, even after the end of ribociclib treatment, for both node-positive and node-negative patients. This is important because NATALEE includes a broad population of patients at risk of recurrence, including those diagnosed with high-risk, node-negative disease who deserve access to new treatment options to reduce that risk."
Regulatory Outlook
Novartis submitted the NATALEE data to the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) in 2023, with FDA regulatory action expected in Q3.
