Addition of Ribociclib Continues to Prolong Survival Among Patients With HR-Positive, HER2-Negative Early Breast Cancer

Extended follow-up results from the phase 3 NATALEE trial demonstrated that the addition of ribociclib to nonsteroidal aromatase inhibitor treatment continued to prolong survival outcomes among patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative early breast cancer. 

“In the second interim NATALEE efficacy analysis, ribociclib plus [ nonsteroidal aromatase inhibitor] demonstrated statistically significant improvement…over [nonsteroidal aromatase inhibitor] alone,” stated Peter Fasching, MD, University Hospital Erlangen, Germany, and coauthors. “Evaluating the efficacy and safety of adjuvant ribociclib beyond the planned 3-year treatment period is critical for understanding the long-term impact on recurrences.”

In this open-label study, 4967 pre- and post-menopausal patients with stage IIA, IIB, or III HR-positive, HER2-negative early breast cancer were randomized on a 1-to-1 basis to receive 2.5 mg of letrozole or 1 mg of anastrozole for up to 60 months either alone (n = 2441) or in combination with 400 mg of ribociclib in 28-day cycles on days 1 through 21 for up to 36 months (n = 2526). Men and premenopausal patients were required to receive 3.6 mg of goserelin once every 28 days. The primary end point was invasive disease-free survival (iDFS). Key secondary end points included distant disease-free survival, recurrence–free survival (RFS), overall survival (OS), and safety. 

At a median follow-up of 44.2 months, the 3-year iDFS rate was 88.1% in the nonsteroidal aromatase inhibitor arm and 90.8% in the ribociclib arm. The 4-year iDFS rates were 83.6% and 88.5%, respectively. Ribociclib improved distant disease-free survival (hazard ratio [HR], 0.72) and RFS (HR, 0.70). OS data were immature at analysis but benefit with ribociclib was observed (HR, 0.83). No new safety signals were identified. The most common all-grade adverse events occurring in the ribociclib arm included neutropenia, arthralgia, and nausea. Adverse events led to ribociclib dose reductions in 23% of patients and ribociclib treatment discontinuation in 20% of patients. No additional treatment-related deaths occurred. 

“NATALEE results continue to support the benefit of adding 3 years of ribociclib to adjuvant [nonsteroidal aromatase inhibitor] in patients with [HR-positive, HER2-negative] early breast cancer at risk of recurrence,” concluded Dr Fasching et al. 

Source: 

Fasching PA, Stroyakovskiy D, Yardley DA, et al. Ribociclib plus endocrine therapy in hormone receptor–positive/ERBB2-negative early breast cancer. JAMA Oncol. Published online: September 25, 2025. doi: 10.1001/jamaoncol.2025.3700