In an updated analysis from the pivotal Phase III NATALEE trial, Novartis' Kisqali (ribociclib) combined with endocrine therapy (ET) demonstrates a sustained and deepening benefit, reducing the risk of recurrence by 28.5% (HR=0.715; 95% CI 0.609–0.840; P <0.0001) in patients with stage II and III hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) early breast cancer (EBC). The data, presented at the European Society for Medical Oncology (ESMO) Congress 2024, highlight the potential of Kisqali to address the significant risk of recurrence in this patient population. This invasive disease-free survival (iDFS) benefit was observed across all pre-specified patient subgroups, including those with node-negative disease.
Sustained iDFS Benefit Across Subgroups
The four-year iDFS rates from the NATALEE trial indicate a clinically meaningful benefit across various subgroups:
- Intention-To-Treat Population: Kisqali + ET: 88.5% vs. ET alone: 83.6% (HR=0.715; 95% CI 0.609–0.840), absolute benefit of 4.9%.
- AJCC Tumor Stage II: Kisqali + ET: 93.9% vs. ET alone: 89.6% (HR=0.644; 95% CI 0.468–0.887), absolute benefit of 4.3%.
- AJCC Tumor Stage III: Kisqali + ET: 84.3% vs. ET alone: 78.4% (HR=0.737; 95% CI 0.611–0.888), absolute benefit of 5.9%.
- Node-negative disease: Kisqali + ET: 92.1% vs. ET alone: 87.0% (HR=0.666; 95% CI 0.397–1.118), absolute benefit of 5.1%.
Consistent Secondary Endpoint Results
Results were consistent across secondary efficacy endpoints, including distant disease-free survival (HR=0.715; 95% CI 0.604–0.847; P <0.0001), with a trend for improvement in overall survival (HR=0.827; 95% CI 0.636–1.074; one-sided P value=0.0766).
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."
Safety Profile
The safety profile of Kisqali remains consistent with previously reported results, with no new safety signals identified. Adverse events (AEs) of special interest (grade 3 or higher) included neutropenia (44.4%), liver-related AEs (e.g., elevated transaminases) (8.6%), and QT interval prolongation (1.0%).
Regulatory Status
Novartis submitted NATALEE data to the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) in 2023, and FDA regulatory action is expected in Q3.
