{"entity":{"id":"paper-natalee-nejm-2024","kind":"paper","name":"NATALEE: three years of ribociclib after surgery in a broad population of hormone-receptor-positive early breast cancer","aka":[],"tldr":"Three years of the CDK4/6 inhibitor ribociclib added to hormone therapy reduced relapses in stage II-III hormone-receptor-positive breast cancer, including some node-negative patients.","summary":"Open-label phase 3 trial of 5,101 patients with hormone-receptor-positive, HER2-negative stage II or III early breast cancer, including node-negative patients with high-risk features, randomised to a non-steroidal aromatase inhibitor with or without three years of ribociclib at a reduced dose (400 mg daily). Primary endpoint was invasive disease-free survival.\n\nThree-year iDFS was 90.4% vs 87.1% (HR 0.75). Together with monarchE it established adjuvant CDK4/6 inhibition, but in a broader, lower-risk population and with a longer, lower-dose schedule.","asOf":"2026-09-08","links":[{"label":"NEJM 2024","url":"https://doi.org/10.1056/NEJMoa2305488"},{"label":"ClinicalTrials.gov NCT03701334","url":"https://clinicaltrials.gov/study/NCT03701334"}],"tags":[],"related":[],"cancers":["breast-hr-positive"],"sections":[],"technologies":["cdk46-inhibitor","endocrine-therapy"],"targets":["cdk4-6","estrogen-receptor"],"drugs":["ribociclib"],"companies":["novartis"],"institutions":[],"pathways":[],"terms":["neoadjuvant-adjuvant","hazard-ratio"],"trials":["natalee","monarche"],"people":["dennis-slamon","im-seock-ah","miguel-martin","loi-sherene","xu-binghe","sara-hurvitz","barrios-carlos"],"bottlenecks":["b-dormancy-mrd","b-drug-pricing","b-dose-optimisation"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2024,"doi":"10.1056/NEJMoa2305488","authors":"Slamon D, Lipatov O, Nowecki Z, et al.","paperType":"rct","findings":["Three-year invasive disease-free survival 90.4% vs 87.1%; HR 0.75 (95% CI 0.62-0.91).","Benefit was consistent across stage II and III and in node-negative and node-positive subgroups.","Distant disease-free survival HR 0.74.","Grade 3 or higher neutropenia in roughly 44% and liver enzyme elevation in roughly 8% of ribociclib patients; about one in five discontinued for adverse events.","Overall survival immature at the primary analysis."],"whatItMeans":"Ribociclib is a second adjuvant CDK4/6 option, and the only one with data in node-negative stage II disease. Roughly 3 in 100 patients avoid a relapse or death at three years, so the decision depends heavily on individual risk, tolerance of a three-year oral drug, and cost. Whether the benefit persists after treatment ends, as it did with abemaciclib, needs longer follow-up.","caveats":["Absolute benefit at three years is about 3 percentage points and the trial included many patients whose baseline risk was modest.","Follow-up beyond the three years of treatment is limited, so durability is not yet established.","Open-label; a large proportion of patients stopped ribociclib early.","Cost of three years of therapy is substantial; cost-effectiveness has been questioned in several health systems."],"changedPractice":true,"participants":5101},"route":"/key-papers/paper-natalee-nejm-2024/","neighbours":{"cancer":[{"id":"hr-positive-early-high-risk","kind":"cancer","name":"High-risk early HR-positive breast cancer","route":"/cancers/hr-positive-early-high-risk/"},{"id":"breast-hr-positive","kind":"cancer","name":"HR-positive / HER2-negative breast cancer","route":"/cancers/breast-hr-positive/"}],"technology":[{"id":"cdk46-inhibitor","kind":"technology","name":"CDK4/6 inhibitors","route":"/technologies/cdk46-inhibitor/"},{"id":"endocrine-therapy","kind":"technology","name":"Endocrine therapy (SERMs, AIs, SERDs)","route":"/technologies/endocrine-therapy/"}],"target":[{"id":"cdk4-6","kind":"target","name":"CDK4/6","route":"/targets/cdk4-6/"},{"id":"estrogen-receptor","kind":"target","name":"Estrogen receptor (ERα)","route":"/targets/estrogen-receptor/"}],"drug":[{"id":"ribociclib","kind":"drug","name":"Ribociclib","route":"/drugs/ribociclib/"}],"company":[{"id":"novartis","kind":"company","name":"Novartis","route":"/companies/novartis/"}],"term":[{"id":"hazard-ratio","kind":"term","name":"Hazard ratio (HR)","route":"/terms/hazard-ratio/"},{"id":"neoadjuvant-adjuvant","kind":"term","name":"Neoadjuvant / adjuvant / perioperative","route":"/terms/neoadjuvant-adjuvant/"}],"trial":[{"id":"monarche","kind":"trial","name":"monarchE","route":"/trials/monarche/"},{"id":"natalee","kind":"trial","name":"NATALEE","route":"/trials/natalee/"}],"person":[{"id":"xu-binghe","kind":"person","name":"Binghe Xu","route":"/people/xu-binghe/"},{"id":"barrios-carlos","kind":"person","name":"Carlos Barrios","route":"/people/barrios-carlos/"},{"id":"dennis-slamon","kind":"person","name":"Dennis J. Slamon","route":"/people/dennis-slamon/"},{"id":"gabriel-hortobagyi","kind":"person","name":"Gabriel N. Hortobagyi","route":"/people/gabriel-hortobagyi/"},{"id":"miguel-martin","kind":"person","name":"Miguel Martín","route":"/people/miguel-martin/"},{"id":"sara-hurvitz","kind":"person","name":"Sara A. Hurvitz","route":"/people/sara-hurvitz/"},{"id":"im-seock-ah","kind":"person","name":"Seock-Ah Im","route":"/people/im-seock-ah/"},{"id":"loi-sherene","kind":"person","name":"Sherene Loi","route":"/people/loi-sherene/"}],"bottleneck":[{"id":"b-dormancy-mrd","kind":"bottleneck","name":"Dormant cells and minimal residual disease","route":"/bottlenecks/b-dormancy-mrd/"},{"id":"b-drug-pricing","kind":"bottleneck","name":"Prices and value","route":"/bottlenecks/b-drug-pricing/"},{"id":"b-dose-optimisation","kind":"bottleneck","name":"Wrong doses","route":"/bottlenecks/b-dose-optimisation/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}]}}