Ribociclib Plus Endocrine Therapy in Hormone Receptor–Positive/ ERBB2 -Negative Early Breast Cancer
Journal
JAMA Oncology
Series/Report No.
JAMA Oncology
Journal Volume
11
Journal Issue
11
Start Page
1364
ISSN
2374-2437
Date Issued
2025-11-01
Author(s)
Fasching, Peter A.
Stroyakovskiy, Daniil
Yardley, Denise A.
Crown, John
Bardia, Aditya
Chia, Stephen
Im, Seock-Ah
Martin, Miguel
Xu, Binghe
Loi, Sherene
Barrios, Carlos
Untch, Michael
Moroose, Rebecca
Visco, Frances
Hortobagyi, Gabriel N.
Slamon, Dennis J.
Fresco, Rodrigo
Zarate, Juan Pablo
Li, Zheng
Waters, Sorcha
Hurvitz, Sara A.
Abstract
Importance: Ribociclib plus a nonsteroidal aromatase inhibitor (NSAI) has demonstrated a statistically significant invasive disease-free survival (iDFS) benefit over NSAI alone in patients with hormone receptor-positive/ERBB2 (formerly HER2)-negative early breast cancer. 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.
Objective: To evaluate efficacy and safety of adjuvant ribociclib in an exploratory 4-year analysis of the NATALEE (New Adjuvant Trial With Ribociclib [LEE011]) randomized clinical trial, with all patients no longer receiving ribociclib treatment.
Design, setting, and participants: This exploratory analysis of an international, open-label, randomized phase 3 trial analyzed adjuvant treatment for premenopausal and postmenopausal women and men with hormone receptor-positive/ERBB2-negative early breast cancer. Eligible patients had anatomic stage IIA (either N0 with additional risk factors or N1 [1-3 axillary lymph nodes]), IIB, or III disease per the American Joint Committee on Cancer Staging Manual, eighth edition. The data cutoff date was April 29, 2024.
Interventions: Patients were randomized 1:1 to receive ribociclib (400 mg once daily, days 1-21 of a 28-day cycle, over 36 months) plus NSAI (letrozole, 2.5 mg, or anastrozole, 1 mg, once daily continuously for 60 months) or NSAI alone. Men and premenopausal women also received goserelin (3.6 mg once every 28 days administered subcutaneously).
Main outcomes and measures: The primary end point was iDFS, and secondary efficacy end points included distant disease-free survival, recurrence-free survival, and overall survival. Survival was evaluated by the Kaplan-Meier method.
Results: Among 5101 patients included in the analysis (median [range] age, 52 [24-90] years; 5081 [99.6%] female), the median follow-up for iDFS was 44.2 months (range, 0-63 months). Ribociclib plus NSAI continued to show iDFS benefit over NSAI alone (hazard ratio, 0.72; 95% CI, 0.61-0.84), with 3-year iDFS rates of 90.8% vs 88.1% (difference, 2.7 percentage points) and 4-year rates of 88.5% vs 83.6% (difference, 4.9 percentage points). The efficacy benefit was consistent across subgroups and secondary end points. Overall survival data remain immature, although a trend in favor of ribociclib plus NSAI over NSAI alone was observed (hazard ratio, 0.83; 95% CI, 0.64-1.07). The incidence of adverse events has remained stable.
Conclusions and relevance: This exploratory analysis of the NATALEE randomized clinical trial, with a median follow-up beyond the 3-year treatment duration, demonstrated consistent iDFS benefit with ribociclib plus NSAI over NSAI alone.
Trial registration: ClinicalTrials.gov Identifier: NCT03701334.
SDGs
Publisher
American Medical Association (AMA)
Type
journal article