{"entity":{"id":"natalee","kind":"trial","name":"NATALEE","aka":[],"tldr":"Extended CDK4/6 inhibitors to a broad group of early hormone-positive breast cancer patients, including node-negative.","summary":"NATALEE, trial NCT03701334 sponsored by Novartis and published in the New England Journal of Medicine in 2023, extended adjuvant CDK4/6 inhibitors to a broad group of stage II to III HR-positive, HER2-negative early breast cancer patients, including those with node-negative disease. It randomised 5,101 patients to three years of ribociclib plus a non-steroidal aromatase inhibitor or the aromatase inhibitor alone, met its primary invasive disease-free survival endpoint at three years with the benefit growing at four years, and led to approval in September 2024. OnCo links it to HR-positive breast cancer, ribociclib, Gabriel N. Hortobagyi, Dennis J. Slamon, the bottleneck of dormant cells and the monarchE and NATALEE papers. Whether three years of a costly drug is justified in lower-risk patients is the open question.","status":"positive","asOf":"2026-09-04","links":[{"label":"ClinicalTrials.gov NCT03701334","url":"https://clinicaltrials.gov/study/NCT03701334"}],"tags":[],"related":[],"cancers":["breast-hr-positive","hr-positive-early-high-risk"],"sections":[],"technologies":["cdk46-inhibitor"],"targets":[],"drugs":["ribociclib"],"companies":["novartis"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["gabriel-hortobagyi","dennis-slamon"],"bottlenecks":[],"keyPapers":["paper-natalee-nejm-2024","paper-natalee-jama-oncol-2025-update"],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT03701334","phase":"3","setting":"Adjuvant ribociclib 3 years + endocrine therapy in stage II-III HR+/HER2- breast cancer","sponsor":"Novartis","result":"iDFS HR 0.75.","started":"2018-12-07","startedType":"actual","yearReported":2023,"enrolled":5101,"enrolledBasis":"registry","outcomes":[{"endpoint":"Invasive disease-free survival at 3 years","primary":true,"unit":"%","arms":[{"name":"Ribociclib + NSAI","n":2549,"value":90.4},{"name":"NSAI alone","n":2552,"value":87.1}],"hr":0.75,"ci":[0.62,0.91],"p":"0.003","source":"https://www.nejm.org/doi/full/10.1056/NEJMoa2305488"},{"endpoint":"Invasive disease-free survival at 4 years","unit":"%","arms":[{"name":"Ribociclib + NSAI","value":88.5},{"name":"NSAI alone","value":83.6}],"hr":0.715,"ci":[0.609,0.84],"source":"https://clinicaltrials.gov/study/NCT03701334"}],"replication":"Consistent with monarchE (abemaciclib) in a broader, lower-risk population; PALLAS and PENELOPE-B (palbociclib) were negative, so the effect is not a uniform class effect."},"route":"/trials/natalee/","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/"}],"drug":[{"id":"ribociclib","kind":"drug","name":"Ribociclib","route":"/drugs/ribociclib/"}],"company":[{"id":"novartis","kind":"company","name":"Novartis","route":"/companies/novartis/"}],"person":[{"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/"}],"paper":[{"id":"paper-monarche-jco-2020","kind":"paper","name":"monarchE: two years of abemaciclib after surgery in high-risk, hormone-receptor-positive early breast cancer","route":"/key-papers/paper-monarche-jco-2020/"},{"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","route":"/key-papers/paper-natalee-nejm-2024/"},{"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","route":"/key-papers/paper-natalee-jama-oncol-2025-update/"}],"term":[{"id":"efs","kind":"term","name":"Event-free / disease-free survival (EFS, DFS, iDFS, RFS)","route":"/terms/efs/"},{"id":"surrogate-validation","kind":"term","name":"Surrogate endpoint validation: which stand-ins have earned trust","route":"/terms/surrogate-validation/"}],"bottleneck":[{"id":"b-dormancy-mrd","kind":"bottleneck","name":"Dormant cells and minimal residual disease","route":"/bottlenecks/b-dormancy-mrd/"}],"roadmap":[{"id":"hormonal-therapy-roadmap","kind":"roadmap","name":"Hormonal therapy roadmap: removing the ovaries → tamoxifen → oral degraders switched by a blood test","route":"/roadmaps/hormonal-therapy-roadmap/"}]}}