# Ribociclib Plus Endocrine Therapy in Hormone Receptor-Positive/ERBB2-Negative Early Breast Cancer: 4-Year Outcomes From the NATALEE Randomized Clinical Trial

Source: https://onco.cc/key-papers/paper-natalee-jama-oncol-2025-update/  
OnCo record `paper-natalee-jama-oncol-2025-update` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Later report from the NATALEE trial registered as NCT03701334, in JAMA Oncology (2025); its title describes an updated or longer-term analysis.

## Summary

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.

Indexed on Europe PMC as PubMed record 40996773 (DOI 10.1001/jamaoncol.2025.3700). Its abstract cites the registry id NCT03701334, which is how it was matched to this trial; no figure has been checked by an editor.

## Fields

- Kind: Key paper
- Last checked: 2026-09-22
- Tags: europepmc-ingest
- Journal: JAMA Oncology
- Year: 2025
- DOI: 10.1001/jamaoncol.2025.3700
- Authors: Fasching PA, Stroyakovskiy D, Yardley DA, et al.
- What it means: A second publication from the NATALEE trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.
- Caveats: Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.; Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper.

## Sources

- JAMA Oncol 2025: https://doi.org/10.1001/jamaoncol.2025.3700
- PubMed: https://pubmed.ncbi.nlm.nih.gov/40996773/
- Europe PMC: https://europepmc.org/article/MED/40996773
- ClinicalTrials.gov NCT03701334: https://clinicaltrials.gov/study/NCT03701334

## Connected records

- trials: [NATALEE](https://onco.cc/trials/natalee/)
- journals: [JAMA Oncology](https://onco.cc/journals/jama-oncology/)

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