The NATALEE trial, which tests adding ribociclib to adjuvant endocrine therapy in hormone receptor-positive, HER2-negative early breast cancer, now reports its prespecified six-year analysis. The central finding is that the combination achieves a statistically significant overall survival benefit over endocrine therapy alone, going beyond the reduction in recurrences already known.
What was known
In its primary analysis, NATALEE had shown that ribociclib plus a nonsteroidal aromatase inhibitor (NSAI) improved invasive disease-free survival compared with NSAI alone in people with HR+/HER2- early breast cancer. It remained to be seen whether that advantage in disease control would translate, with longer follow-up, into an overall survival benefit, the outcome that matters most in the long term.
What this work adds
This is the prespecified descriptive six-year analysis of the phase 3 trial, with a median overall survival follow-up of 66.5 months. Participants were adults with HR+/HER2- early breast cancer at anatomic stage IIA (N1, or N0 with high-risk features), IIB or III. They were randomised 1:1 to ribociclib 400 mg daily (three weeks on, one off, for three years) plus an NSAI — letrozole 2.5 mg or anastrozole 1 mg daily for five years — or NSAI alone; premenopausal women and men also received goserelin. The primary endpoint was invasive disease-free survival.
Main results
The combination of ribociclib and an NSAI showed an overall survival benefit over NSAI alone: the absolute difference at six years was 2.1%, with a hazard ratio (HR) of 0.809 (95% confidence interval 0.661-0.989; nominal one-sided P = 0.019). The effect was broadly consistent across key subgroups. An increasing benefit in invasive disease-free survival was also observed, with an absolute difference at six years of 5.3% and an HR of 0.741 (95% CI 0.646-0.849).
What it means
The overall survival benefit reinforces the role of adjuvant ribociclib in the broad population defined by NATALEE and fits with the growing reduction in recurrence risk accumulating over follow-up. For patients, it means that the three-year oral treatment not only delays recurrences but translates into a modest yet real survival gain at six years; the 2.1% absolute difference helps to size it without overstating it.
A view from the breast unit
A three-year ribociclib schedule plus five years of endocrine therapy calls for planning: education about the cycle, management of adverse effects, long-term adherence and coordinated follow-up with primary care. The breast unit is the natural setting for that support and for explaining what each patient gains and what she commits to.
Reference: Slamon DJ, Hortobagyi GN, Stroyakovskiy D, Yardley DA, Huang CS, Crown J, et al. Overall survival with adjuvant ribociclib plus nonsteroidal aromatase inhibitor in patients with high-risk HR+/HER2- early breast cancer: Six-year follow-up of the NATALEE trial. Annals of Oncology, 2026. DOI
