Novartis Kisqali® reduces early breast cancer recurrence risk by 28.5% in broad patient population

In a significant development from the Phase III NATALEE trial, the investigational drug Kisqali® (ribociclib), when combined with endocrine therapy (ET), has demonstrated a marked enhancement in reducing the risk of cancer recurrence. The combination therapy achieved a 28.5% reduction in recurrence risk compared to ET alone for patients with stage II and III hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) early breast cancer (EBC). This advancement is particularly noteworthy as it extends the treatment benefit beyond the three-year period initially set for the therapy.

The four-year post-hoc analysis presented at the European Society for Medical Oncology (ESMO) Congress 2024, highlights the sustained invasive disease-free survival (iDFS) benefit of Kisqali. This benefit remained consistent across all pre-specified patient subgroups, including those with node-negative disease. The iDFS rates for Kisqali combined with ET were notably higher than ET alone across several subgroups:

- The overall intention-to-treat population showed an iDFS rate of 88.5% for Kisqali + ET versus 83.6% for ET alone.
- For patients with AJCC Tumor Stage II, the iDFS rate was 93.9% for Kisqali + ET compared to 89.6% for ET alone.
- In AJCC Tumor Stage III patients, the iDFS rate was 84.3% for Kisqali + ET versus 78.4% for ET alone.
- Among those with node-negative disease, the rate was 92.1% for Kisqali + ET compared to 87.0% for ET alone.

The consistency of results across secondary efficacy endpoints, including distant disease-free survival, further underscores the effectiveness of Kisqali. A trend towards improved overall survival was also observed.

Peter A. Fasching, M.D., a NATALEE trial investigator and Professor of Translational Medicine at the University Hospital Erlangen, emphasized the importance of addressing the high risk of recurrence in HR+/HER2- early-stage breast cancer. He noted that the continued benefit of ribociclib, even post-treatment, is critical for both node-positive and node-negative patients.

The safety profile of Kisqali remained consistent with previous reports, showing no new safety signals. Adverse events of special interest included neutropenia (44.4%), liver-related adverse events (8.6%), and QT interval prolongation (1.0%).

Shreeram Aradhye, M.D., President of Development and Chief Medical Officer at Novartis, expressed optimism about these long-term results. He highlighted the importance of these findings for a large population of HR+/HER2- early breast cancer patients who remain at risk of recurrence. The company is hopeful that Kisqali will soon be recognized as a significant addition to the treatment options available for these patients, particularly those with node-negative disease.

The NATALEE trial, a global Phase III study, involved 5,101 adult patients with HR+/HER2- EBC across 20 countries. The primary endpoint was iDFS, as defined by Standardized Definitions for Efficacy End Points (STEEP) criteria. The trial compared the efficacy and safety of ribociclib with ET against ET alone.

Kisqali, a selective cyclin-dependent kinase inhibitor, targets CDK4/6 proteins to slow cancer progression by preventing the rapid division of cancer cells. Regulatory reviews for Kisqali as an early breast cancer treatment are ongoing worldwide, with the U.S. FDA expected to take action in Q3.

Kisqali is already approved for metastatic breast cancer in 99 countries. In the U.S., it is indicated for HR+/HER2- advanced or metastatic breast cancer in combination with an aromatase inhibitor or fulvestrant. The drug has shown significant overall survival benefits across multiple Phase III trials and is recommended as a first-line treatment option in the NCCN Guidelines® for breast cancer.

Novartis continues to lead in breast cancer treatment innovations, with a comprehensive portfolio and ongoing research collaborations aimed at improving clinical practice and patient outcomes.