Adjuvant ribociclib plus nonsteroidal aromatase inhibitor therapy in patients with HR-positive/HER2-negative early breast cancer: 5-year follow-up of NATALEE efficacy outcomes and updated overall survival
Journal
ESMO Open
Series/Report No.
ESMO Open
Journal Volume
10
Journal Issue
11
Start Page
105858
ISSN
2059-7029
Date Issued
2025-11
Author(s)
Crown, J.
Stroyakovskii, D.
Yardley, D.A.
Fasching, P.A.
Bardia, A.
Chia, S.
Im, S.-A.
Martin, M.
Xu, B.
Barrios, C.H.
Untch, M.
Moroose, R.
Hurvitz, S.A.
Hortobagyi, G.N.
Slamon, D.J.
Visco, F.
Spera, G.
Zarate, J.P.
Halligan, D.
Li, Z.
Loi, S.
Abstract
Background: At the primary efficacy analysis of the NATALEE phase III trial, ribociclib plus a nonsteroidal aromatase inhibitor (NSAI) demonstrated a statistically significant improvement in invasive disease-free survival (iDFS) versus NSAI alone in patients with hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative early breast cancer (EBC). Continued follow-up of efficacy outcomes is important in assessing the durability of treatment benefit. We report 5-year estimates of efficacy outcomes, including an udpated analysis of overall survival (OS).
Patients and methods: Eligible patients included pre/postmenopausal women and men with HR-positive/HER2-negative EBC and anatomic stage IIA (N1 or N0 with high-risk factors), IIB, or III disease. Patients were randomized 1 : 1 to ribociclib 400 mg/day (3 weeks on/1 week off for 3 years) + NSAI (letrozole 2.5 mg/day or anastrozole 1 mg/day for 5 years) or NSAI alone. Premenopausal women and men received goserelin. The primary endpoint was iDFS, and secondary/exploratory endpoints included distant disease-free survival, recurrence-free survival, distant recurrence-free survival, and OS.
Results: With a median iDFS follow-up of 55.4 months, ribociclib + NSAI demonstrated persistent iDFS benefit versus NSAI alone [hazard ratio 0.716, 95% confidence interval (CI) 0.618-0.829, nominal one-sided log-rank P < 0.0001]. Absolute iDFS improvement between treatment arms increased from the 3- (Δ2.7%) to the 5-year (Δ4.5%) time points. Persistent benefit over time was also observed across subgroups [including N0 patients (hazard ratio 0.606, 95% CI 0.372-0.986)] and secondary/exploratory endpoints. As OS continues to mature, numerical improvement in favor of ribociclib was observed (hazard ratio 0.800, 95% CI 0.637-1.003, nominal one-sided log-rank P = 0.026).
Conclusions: This prespecified 5-year follow-up of efficacy outcomes from NATALEE demonstrated that ribociclib + NSAI continued to reduce the risk of recurrence beyond the 3-year treatment window, supporting its use as adjuvant therapy in patients with HR-positive/HER2-negative EBC. An ongoing positive trend for improved OS in favor of ribociclib + NSAI was observed.
Subjects
CDK4/6 inhibitor
HR positive/HER2 negative
NATALEE
early breast cancer
ribociclib
SDGs
Publisher
Elsevier BV
Type
journal article