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

Crown J, Stroyakovskii D, Yardley DA, Huang CS, Fasching P, Bardia A, Chia S, Im SA, Martin M, Xu B, Barrios CH, Untch M, Moroose R, Hurvitz SA, Hortobagyi GN, Slamon DJ, Visco F, Spera G, Zarate JP, Halligan D, Li Z, Loi S (2025)

Publication Type: Journal article

Publication year: 2025

Journal

Book Volume: 10

Article Number: 105858

Journal Issue: 11

DOI: 10.1016/j.esmoop.2025.105858

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.

Authors with CRIS profile

Involved external institutions

Moscow City Oncology Hospital №62 Russian Federation (RU) Novartis Ireland Limited Ireland (IE) St Vincent's University Hospital Ireland (IE) Universidad Complutense de Madrid (UCM) Spain (ES) University of California Los Angeles (UCLA) United States (USA) (US) Novartis AG Switzerland (CH) University of Washington United States (USA) (US) National Breast Cancer Coalition NBCC United States (USA) (US) British Columbia Cancer Agency Canada (CA) Orlando Health United States (USA) (US) National Taiwan University Hospital (NTUH) / 國立台灣大學醫學院附設醫院 Taiwan (TW) Peter MacCallum Cancer Centre Australia (AU) University of Texas MD Anderson Cancer Center United States (USA) (US) TRIO - Translational Research In Oncology Canada (CA) HELIOS Kliniken Germany (DE) Sarah Cannon Research Institute (SCRI) United States (USA) (US) Seoul National University (SNU) / 서울대학교 Korea, Republic of (KR) Peking Union Medical College / 北京协和医学院 China (CN) LACOG - Latin American Cooperative Oncology Group Brazil (BR)

How to cite

APA:

Crown, J., Stroyakovskii, D., Yardley, D.A., Huang, C.S., Fasching, P., Bardia, A.,... Loi, S. (2025). 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. ESMO Open, 10(11). https://doi.org/10.1016/j.esmoop.2025.105858

MLA:

Crown, J., et al. "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." ESMO Open 10.11 (2025).

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