Early, High-Risk Breast Cancer: Expanded FDA Approval for CDK4/6 Inhibitor–Based Therapy

By: JNCCN 360 Staff
Posted: Thursday, September 19, 2024

On September 17, the U.S. Food and Drug Administration (FDA) approved the CDK4/6 inhibitor ribociclib (Kisqali) in combination with an aromatase inhibitor (AI) for the adjuvant treatment of adults with hormone receptor (HR)-positive, HER2-negative stage II and III early-stage breast cancer who are at high risk of recurrence, including those with node-negative disease. Also approved was the ribociclib and letrozole co-pack (Kisqali Femara Co-Pack) for the same indication.

This approval is based on results from the randomized, open-label, phase III NATALEE trial (ClinicalTrials.gov identifier NCT03701334), which involved 5,101 adults with HR-positive, HER2-negative early-stage breast cancer across 20 countries. Participants were randomly assigned (1:1) to receive 400 mg of ribociclib plus a nonsteroidal aromatase inhibitor (NSAI) or an NSAI alone.

At the interim analysis, a statistically significant improvement in invasive disease–free survival was reported in the intent-to-treat population. At the final invasive disease–free survival analysis, invasive disease–free survival at 36 months was 90.7% (95% confidence interval [CI] = 89.3%–91.8%) with ribociclib and 87.6% (95% CI = 86.1%–88.9%) without it, for a hazard ratio of 0.749 (95% CI = 0.628–0.892). At the time of the invasive disease–free survival final analysis, overall survival data were immature.

Adverse events observed in the NATALEE trial were found to be consistent with the current safety profile for this combination therapy. They included neutropenia, liver-related adverse events, QT interval prolongation, and interstitial lung disease/pneumonitis.

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