Treatment Outcomes of Patients with Early-Stage Breast Cancer Meeting NATALEE Eligibility Criteria. A Real-World Cohort Study

Abstract

Purpose Adjuvant CDK4/6 inhibitors have demonstrated significant disease-free survival (DFS) benefits in high-risk early-stage hormone receptor (HR)-positive /HER2-negative breast cancer. However, real-world outcome data describing patients who would meet contemporary eligibility criteria remain limited. This study evaluates treatment outcomes in patients retrospectively classified as eligible for adjuvant ribociclib treatment. Patients and Methods A retrospective cohort analysis was conducted using clinical data from patients with early-stage HR-positive/HER2-negative breast cancer. Eligibility for adjuvant ribociclib was assigned using the NATALEE trial-based criteria. Differences in treatment outcomes in those eligible versus ineligible patients are reported. Results Among the 2730 patients included, 1,955 (71.6%) were high risk and would have met NATALEE eligibility, including 1,679 (85.9%) with node-positive disease, 602 (30.8%) with cT3-4 tumors, and 686 (35.1%) with grade 3 disease; 775 (28.4%) were ineligible due to lower-risk features. Across the cohort, the 5-year DFS rate was significantly worse in CDK4/6i-eligible patients compared to those deemed ineligible: 78.4% versus 91.5% (HR=2.51; 95% CI: 2.01–3.14; p<0.0001). Though median OS was not reached, survival curve separation became evident by 36 months and widened progressively. Multivariable Cox regression identified low/intermediate ER expression (<50%), node-positive disease, larger tumors (cT3-4), and grade 3 histology as independent predictors of worse overall survival. Low/intermediate ER expression was associated with significantly poorer OS (HR 1.85, 95% CI 1.27–2.70; p=0.001), while lower-grade and smaller tumors were associated with improved survival. Conclusion A significant proportion of patients in this real-world cohort would have met criteria for adjuvant CDK4/6 inhibition. These patients experienced worse survival outcomes compared to their ineligible counterparts. These findings provide real-world historical outcome data for patients who would now be considered candidates for adjuvant ribociclib and may serve as a benchmark for evaluating outcomes following adoption of adjuvant ribociclib.