Key Insights From the NATALEE Trial
Key Points
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Ribociclib plus endocrine therapy significantly improved invasive disease–free survival compared with endocrine therapy alone in the adjuvant setting.
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The NATALEE trial enrolled a broader population of patients with early-stage, hormone receptor–positive, HER2-negative breast cancer.
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With extended follow-up, NATALEE supports earlier use of CDK4/6 inhibitors to reduce the risk of recurrence in appropriately selected patients.
Emerging clinical trial data presented at the 2025 San Antonio Breast Cancer Symposium are reshaping adjuvant treatment strategies in breast cancer. During the conference, Karissa Britten, MD, of Cedars-Sinai Cancer, joined Matthew Kurian, MD, of St. Elizabeth Healthcare, to discuss trial updates with a focus on the 5-year data from the NATALEE study.
The phase 3 trial evaluated ribociclib, a CDK4/6 inhibitor, in combination with standard endocrine therapy as an adjuvant treatment for patients with hormone receptor–positive, HER2-negative early breast cancer. Unlike prior adjuvant CDK4/6 studies, NATALEE included a broader risk population, enrolling patients with stage II and III disease, including some node-negative patients with high-risk clinical features.
Data published in 2024 showed improvements in invasive disease-free survival (IDFS), the study’s primary end point, and distant disease-free survival. The subsequent FDA approval was notable, according to Dr. Britten, as monarchE had previously been the only positive adjuvant CDK4/6 trial, and ribociclib offered a different dosing schedule and toxicity profile, expanding treatment options in this setting.
More recently, overall survival (OS) data from both monarchE and NATALEE were presented, providing additional reassurance for clinicians. Before these updates, many clinicians reserved ribociclib for patients who did not meet monarchE eligibility criteria or who could not tolerate abemaciclib, said Dr. Britten.
Both clinicians also highlighted the challenges of cross-trial comparisons, given differences in patient populations and statistical design, and emphasized that NATALEE was not powered for OS. However, the 5-year data showing a significant improvement in IDFS supports ribociclib as an effective adjuvant option and expands the role of CDK4/6 inhibition beyond the metastatic setting.