Episode 16: The NATALEE trial: ribociclib as a key adjuvant CDK4/6 Inhibitor for breast cancer

In this episode of WND Breast, Dr Kevin Punie from GZA Hospitals and Prof Evandro de Azambuja from Institut Jules Bordet will delve into the NATALEE trial, contributing insights to adjuvant CDK4/6 inhibitors in breast cancer patients.

The NATALEE trial is a phase 3 study, in which approximately 5,100 patients are randomized to receive either endocrine therapy alone or in combination with ribociclib over 3 years. The trial enrolled high-risk patients with node-positive disease and some node-negative patients exhibiting high-risk features such as high gene expression profiles or high KI67 levels.

Initial analysis of the trial demonstrated a 3% improvement in Invasive Disease-Free Survival (IDFS) and a 2% improvement in Distant Recurrence-Free Survival (DRFS) among nearly 20% of the patient cohort. However, treatment discontinuation due to toxicity affected approximately 18% of patients, prompting questions about real-world applicability despite positive outcomes.

The updated analysis by an additional 5.6 months follow-up with more patients completing the treatment revealed a prolongation of the final Invasive Disease-Free Survival (IDFS). They continue to show improvements with a slight increase in the magnitude of benefit, reaching about 4% for both IDFS and 3% DRFS.

The key message underscores the efficacy of CDK4/6 inhibitors, demonstrated by ribociclib over 3 years in the NATALEE trial and abemaciclib over 2 years in the MonarchE trial, in enhancing patient outcomes. While OS data are pending for both trials, approval of ribociclib treatment in the adjuvant setting is anticipated.

This will offer different treatment options for high-risk and intermediate-risk patients, with treatment duration considerations tailored to individual patient risk factors, including profile, comorbidities, and concurrent medications. Comparative analysis of both trials regarding treatment duration and patient benefit presents challenges, especially for patients with node-positive disease. Abemaciclib is linked to side effects like diarrhoea, whereas ribociclib is associated with hepatic toxicity and QT prolongation, underscoring the importance of judicious treatment selection based on patient profiles.

CDK4/6 inhibitors as a novel treatment option are anticipated without necessitating further increases in benefit magnitude. As in the metastatic setting, physician preferences between ribociclib and abemaciclib are expected to be the scenario in the adjuvant setting.