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, PA; 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

Author(s): Crown, J; Stroyakovskii, D; Yardley, DA; Huang, CS; Fasching, PA; 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;
Details: Publication Year 2025-11,Volume 10,Issue #11,Page 105858
Journal Title: ESMO Open
Publication Type: Research article
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.
Publisher: Elsevier
Keywords: Humans; *Aminopyridines/therapeutic use/administration & dosage; *Purines/therapeutic use/administration & dosage; Female; *Aromatase Inhibitors/therapeutic use/administration & dosage; *Breast Neoplasms/drug therapy/mortality/pathology; Middle Aged; Male; Follow-Up Studies; Receptor, ErbB-2/metabolism; Aged; Adult; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use; Treatment Outcome; Chemotherapy, Adjuvant/methods; Receptors, Progesterone/metabolism; Receptors, Estrogen/metabolism; Letrozole/administration & dosage/therapeutic use; CDK4/6 inhibitor; HR positive/HER2 negative; Natalee; early breast cancer; ribociclib
Department(s): Medical Oncology
Publisher's Version: https://doi.org/10.1016/j.esmoop.2025.105858
Open Access at Publisher's Site: https://doi.org/10.1016/j.esmoop.2025.105858
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2026-01-06 02:46:50

Last Modified: 2026-01-06 02:47:11