Background
Despite improvements in outcomes in patients with hormone receptor–positive early breast cancer, distant recurrence remains a major concern given that there is no cure for metastatic breast cancer. The NATALEE trial has shown invasive disease-free survival (iDFS) and distant disease-free survival (DDFS) benefits with ribociclib plus a nonsteroidal aromatase inhibitor (NSAI) in patients with stage II/III hormone receptor–positive/HER2-negative (HER2–) early breast cancer. We present updated DDFS from the prespecified 5-year landmark analysis of NATALEE across clinically relevant subgroups.
Methods
Patients were randomly assigned 1:1 to receive ribociclib plus NSAI or NSAI alone. Patients with anatomic stage IIA (either node-negative [N0] with additional risk factors or N1 [1-3 axillary lymph nodes]), IIB, or III disease per AJCC (8th edition) were included. DDFS, a secondary end point, was defined as the time from randomization to first event of distant recurrence, second primary non-breast invasive cancer (except basal/squamous cell skin carcinomas), or death from any cause. Kaplan-Meier analysis was used to estimate survival rates; a Cox proportional hazards model was applied to calculate hazard ratios (HRs) for ribociclib plus NSAI vs NSAI alone, stratified based on study stratification factors. DDFS was analyzed across clinically relevant subgroups, including anatomic stage and nodal status.
Results
At data cutoff (May 28, 2025; median follow-up for DDFS, 55.5 months), ribociclib plus NSAI continued to show DDFS benefit (HR, 0.709; 95% CI: 0.608-0.827; nominal 1-sided P <.0001) and distant recurrence-free survival benefit (HR, 0.699; 95% CI: 0.594-0.824; nominal 1-sided P<.0001) over NSAI alone in the intent-to-treat population. The most common sites of distant recurrence were bone, liver, lung/pleura, and lymph nodes with fewer events observed with RIB+NSAI vs NSAI alone. DDFS benefit was observed irrespective of anatomic stage (Table). A consistent improvement in DDFS with ribociclib plus NSAI vs NSAI alone was observed irrespective of nodal status (Table). DDFS benefit with ribociclib plus NSAI was similar across other relevant subgroups (menopausal status, age, prior endocrine therapy duration, and Ki-67 status).
Conclusions
In this prespecified 5-year analysis, with all patients off ribociclib (median=2 years), DDFS benefit with ribociclib plus NSAI was sustained/improved compared with prior NATALEE analyses. This benefit was observed across all key subgroups, including N0 disease. These findings support the use of adjuvant ribociclib plus NSAI to reduce distant recurrence risk in the NATALEE-eligible high-risk hormone receptor–positive/HER2− early breast cancer population.
Previously presented at 2025 SABCS: Hurvitz S, et al. December 9-12, 2025; San Antonio, TX. Poster PS3-09-08. Reused with permission.
