Novartis has secured European Commission (EC) approval for Kisqali (ribociclib) in combination with an aromatase inhibitor (AI) for the adjuvant treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative early breast cancer (EBC) patients at high risk of recurrence. This decision, based on the pivotal Phase III NATALEE trial, marks a significant advancement in addressing the unmet needs of a broad population of EBC patients.
The NATALEE trial, a multi-center, randomized, open-label study, involved 5,101 patients across 20 countries. The results demonstrated a clinically meaningful 25.1% reduction in the risk of disease recurrence with adjuvant Kisqali plus endocrine therapy (ET) compared to ET alone (HR=0.749; 95% CI: 0.628, 0.892; P=0.0006). This invasive disease-free survival (iDFS) benefit was consistently observed across all patient subgroups, including those with node-negative disease.
Clinical Impact and Expert Opinions
Michael Gnant, M.D., Professor of Surgery at the Medical University of Vienna, emphasized the importance of this approval, stating, "This approval represents a positive milestone for the early breast cancer community in Europe, including physicians who now have a new option to help reduce the risk of recurrence in a broader population of patients."
Michael Untch, M.D., Professor and Head of the Clinic for Gynecology and Obstetrics, added, "Adding a new treatment option to the HR+/HER2- early breast cancer armamentarium is encouraging news for both physicians and their patients – including patients with node-negative disease and additional risk factors. Ribociclib may now help many patients who are at risk of their cancer returning."
Addressing Unmet Needs in Early Breast Cancer
Breast cancer is the most commonly diagnosed cancer in Europe, with approximately 70% of cases diagnosed in the early stages. Despite current treatment options, a significant proportion of patients with stage II and III HR+/HER2- EBC remain at risk of experiencing a return of their cancer in the long term, often as incurable advanced disease. The approval of Kisqali aims to minimize this risk and improve health outcomes for a broader patient population.
Kisqali: Mechanism of Action and Global Approvals
Kisqali (ribociclib) is a selective cyclin-dependent kinase inhibitor that works by slowing cancer progression through the inhibition of CDK4 and CDK6 proteins. It has been approved for breast cancer treatment in over 100 countries worldwide.
NATALEE Trial Details
The Phase III NATALEE trial included a broad patient population with HR+/HER2- stage II and III EBC, including those with node-negative disease. The primary endpoint of the trial was invasive disease-free survival (iDFS), as defined by the Standardized Definitions for Efficacy End Points (STEEP) criteria. The adjuvant ET in both treatment arms was a non-steroidal aromatase inhibitor (NSAI; anastrozole or letrozole) and goserelin if applicable.
Regulatory Landscape and Future Directions
This approval follows the recent U.S. Food and Drug Administration (FDA) approval of Kisqali for EBC patients and its recommendation as a Category 1 preferred breast cancer adjuvant treatment by the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (NCCN Guidelines). Regulatory reviews of Kisqali for EBC are ongoing worldwide, and Novartis will continue evaluating NATALEE trial patients for long-term outcomes, including overall survival.
