The NCCN Clinical Practice Guidelines in Oncology have updated their recommendations to include ribociclib (Kisqali) as a Category 1 preferred CDK4/6 inhibitor adjuvant therapy for patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) early breast cancer (EBC) in combination with an aromatase inhibitor (AI). This designation applies to both node-positive and high-risk node-negative patients, aligning with the findings from the Phase III NATALEE trial and the recent FDA approval.
Clinical Evidence and Guideline Updates
The Category 1 recommendation signifies a high level of clinical evidence and a uniform consensus among NCCN experts regarding the appropriateness of ribociclib for these patients. The decision follows the presentation of long-term results from the NATALEE trial at the European Society for Medical Oncology (ESMO) Congress 2024, demonstrating sustained efficacy beyond the treatment duration, even in node-negative patients. Shreeram Aradhye, M.D., President, Development and Chief Medical Officer, Novartis, stated, "These evidence-based guidelines are helpful to clinicians when determining optimal treatment options for patients," emphasizing the importance of offering ribociclib to eligible early breast cancer patients to reduce recurrence risk.
Impact on Patient Population
The updated guidelines, consistent with the FDA indication based on the NATALEE trial, are expected to approximately double the number of patients who could benefit from CDK4/6 inhibitor treatment in the adjuvant setting. This expansion includes patients with limited nodal involvement and high-risk N0 disease, such as those with tumors larger than 5 cm, or tumors sized 2-5 cm with Grade 2 and high genomic risk/Ki-67 ≥20%, or Grade 3.
Continued Recommendation for Metastatic Breast Cancer
In addition to the adjuvant setting, the NCCN Guidelines continue to recommend ribociclib as the only Category 1 preferred CDK4/6 inhibitor for first-line treatment of patients with HR+/HER2- metastatic breast cancer in combination with an AI. Ribociclib is also a Category 1 preferred regimen for first- and subsequent-line therapies in HR+/HER2- MBC in combination with fulvestrant, if a CDK4/6 inhibitor was not previously used.
About Ribociclib (Kisqali)
Ribociclib is a selective cyclin-dependent kinase inhibitor that targets CDK4 and CDK6 proteins, which, when over-activated, can promote uncontrolled cancer cell growth. By inhibiting these proteins, ribociclib helps slow cancer progression. It is approved for metastatic breast cancer in 99 countries, including the US and the European Union, and has demonstrated statistically significant overall survival benefits across three Phase III trials in MBC.
