122 Adjuvant Ribociclib (RIB) Plus Nonsteroidal Aromatase Inhibitor (NSAI) in Patients With HR+/HER2− Early Breast Cancer (EBC): NATALEE 5-Year Outcomes

Background

The phase 3 NATALEE trial demonstrated that adjuvant ribociclib plus nonsteroidal aromatase inhibitor (NSAI) led to a statistically significant invasive disease–free survival (iDFS) benefit in patients with stage II and III hormone receptor–positive/HER2-negative early breast cancer. We present a protocol-specified 5-year efficacy analysis.

Methods

Patients with hormone receptor–positive/HER2-negative early breast cancer were randomly assigned 1:1 to ribociclib (400 mg/d; 3 weeks on/1 week off for 3 years) plus NSAI (letrozole 2.5 mg/day or anastrozole 1 mg/day for 5 years) or NSAI alone. Men and premenopausal women received goserelin. Patients were included if they had anatomical stage IIA (if N1 [1-3 axillary lymph nodes] or N0 with additional high-risk factors), stage IIB, or stage III disease per AJCC, 8th ed. The primary end point of iDFS and secondary efficacy end points of distant disease–free survival (DDFS), distant relapse–free survival (DRFS), and overall survival (OS) were evaluated using Kaplan-Meier methods. Statistical comparisons were made by stratified log-rank test.

Results

At data cutoff (May 28, 2025), all patients were off ribociclib treatment, and a similar proportion had completed 5 years of NSAI treatment in both arms (ribociclib plus NSAI, 36.5%; NSAI alone, 34.4%). With a median iDFS follow-up of 55.4 months, ribociclib plus NSAI demonstrated persistent iDFS benefit over NSAI alone (HR, 0.716; 95% CI, 0.618-0.829; nominal 1-sided P <.0001). Absolute iDFS rates were 90.8% vs 88.0% at 3 years, 88.3% vs 83.9% at 4 years, and 85.5% vs 81.0% at 5 years (absolute improvement of 2.7%, 4.4%, and 4.5%, respectively). iDFS benefit was observed across subgroups, including N0 (HR, 0.606; 95% CI, 0.372-0.986). Ribociclib plus NSAI also demonstrated continued DDFS (HR, 0.709; 95% CI, 0.608-0.827) and DRFS (HR, 0.699; 95% CI, 0.594-0.824) benefit vs NSAI alone. A positive trend for OS favoring ribociclib plus NSAI (HR, 0.800; 95% CI, 0.637-1.003; nominal 1-sided P = .026) continues to emerge. No new safety signals were observed with a median follow-up time of approximately 2 years after ribociclib completion.

Conclusions

In this 5-year landmark analysis with mature efficacy data, ribociclib plus NSAI reduced the risk of invasive and distant disease recurrence compared with NSAI alone, including in patients with high-risk N0 disease. A positive trend for OS in favor of ribociclib plus NSAI continues to emerge.

Previously presented at 2025 ESMO: Crown J, et al. October 17-21, 2025; Berlin, Germany. LBA14. Reused with permission.