{"entity":{"id":"paper-natalee-jama-oncol-2025-update","kind":"paper","name":"Ribociclib Plus Endocrine Therapy in Hormone Receptor-Positive/ERBB2-Negative Early Breast Cancer: 4-Year Outcomes From the NATALEE Randomized Clinical Trial","aka":[],"tldr":"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.\n\nObjective: 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.\n\nDesign, 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.\n\nInterventions: 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).\n\nMain 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.\n\nResults: 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.\n\nConclusions 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.\n\nTrial registration: ClinicalTrials.gov Identifier: NCT03701334.\n\nIndexed 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.","asOf":"2026-09-22","links":[{"label":"JAMA Oncol 2025","url":"https://doi.org/10.1001/jamaoncol.2025.3700"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40996773/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/40996773"},{"label":"ClinicalTrials.gov NCT03701334","url":"https://clinicaltrials.gov/study/NCT03701334"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["natalee"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2025,"doi":"10.1001/jamaoncol.2025.3700","pmid":"40996773","authors":"Fasching PA, Stroyakovskiy D, Yardley DA, et al.","paperType":"rct","findings":[],"whatItMeans":"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."]},"route":"/key-papers/paper-natalee-jama-oncol-2025-update/","neighbours":{"trial":[{"id":"natalee","kind":"trial","name":"NATALEE","route":"/trials/natalee/"}],"journal":[{"id":"jama-oncology","kind":"journal","name":"JAMA Oncology","route":"/journals/jama-oncology/"}]}}