{"entity":{"id":"paper-monarche-jco-2020","kind":"paper","name":"monarchE: two years of abemaciclib after surgery in high-risk, hormone-receptor-positive early breast cancer","aka":[],"tldr":"Adding two years of the CDK4/6 inhibitor abemaciclib to standard hormone therapy after surgery cut the risk of the cancer coming back by a quarter in women with node-positive, high-risk disease.","summary":"Open-label phase 3 trial of 5,637 patients with hormone-receptor-positive, HER2-negative early breast cancer at high risk of recurrence (four or more positive nodes, or one to three nodes with grade 3, tumour 5 cm or more, or high Ki-67), randomised to standard endocrine therapy with or without two years of abemaciclib. Primary endpoint was invasive disease-free survival (iDFS).\n\nAt the pre-planned interim analysis, iDFS was improved (HR 0.75; 2-year iDFS 92.2% vs 88.7%). The benefit widened with time: at five years iDFS was 83.6% vs 76.0%, a 7.6-point absolute difference (HR 0.68), well after abemaciclib had stopped. It was the first adjuvant CDK4/6 inhibitor to succeed after palbociclib failed in PALLAS and PENELOPE-B.","asOf":"2026-09-08","links":[{"label":"PubMed search: monarchE JCO 2020","url":"https://pubmed.ncbi.nlm.nih.gov/?term=monarchE+abemaciclib+adjuvant+Johnston+2020"},{"label":"ClinicalTrials.gov NCT03155997","url":"https://clinicaltrials.gov/study/NCT03155997"}],"tags":[],"related":[],"cancers":["breast-hr-positive"],"sections":[],"technologies":["cdk46-inhibitor","endocrine-therapy"],"targets":["cdk4-6","estrogen-receptor"],"drugs":["abemaciclib"],"companies":["eli-lilly"],"institutions":[],"pathways":[],"terms":["neoadjuvant-adjuvant","hazard-ratio"],"trials":["monarche","natalee"],"people":["miguel-martin","shao-zhi-ming","sohn-joohyuk","javier-cortes","andrew-wardley","sara-tolaney"],"bottlenecks":["b-dormancy-mrd","b-drug-pricing","b-toxicity-qol"],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2020,"doi":"10.1200/JCO.20.02514","pmid":"32954927","authors":"Johnston SRD, Harbeck N, Hegg R, et al.","paperType":"rct","findings":["Invasive disease-free survival HR 0.75 (95% CI 0.60-0.93) at the interim analysis; 2-year iDFS 92.2% vs 88.7%.","Five-year update (2024): iDFS 83.6% vs 76.0% (HR 0.68) and distant relapse-free survival 86.0% vs 79.2%, with the curves continuing to separate after treatment ended.","Diarrhoea occurred in over 80% of abemaciclib patients (mostly grade 1-2) and roughly one in six discontinued because of adverse events.","Ki-67 of 20% or more identified a higher-risk group but did not predict a larger relative benefit, so the label was later broadened to all high-risk node-positive patients.","Overall survival data remain immature."],"whatItMeans":"Women with hormone-receptor-positive, HER2-negative breast cancer that has spread to lymph nodes and has other high-risk features can now be offered two years of abemaciclib alongside their hormone therapy, with a durable reduction in relapse. It does not apply to node-negative or low-risk disease, and the diarrhoea and cost are real trade-offs to discuss.","caveats":["No overall survival benefit has yet been shown.","Open-label design with an endpoint (iDFS) that includes second primary cancers.","The contrast with the negative PALLAS trial (palbociclib) is not fully explained: differences in drug, dose intensity, or population selection are all possible.","Two years of a costly oral drug for a 7-8 point absolute gain raises access questions in many health systems."],"changedPractice":true,"participants":5637},"route":"/key-papers/paper-monarche-jco-2020/","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":"abemaciclib","kind":"drug","name":"Abemaciclib","route":"/drugs/abemaciclib/"}],"company":[{"id":"eli-lilly","kind":"company","name":"Eli Lilly (incl. Loxo)","route":"/companies/eli-lilly/"}],"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":"andrew-wardley","kind":"person","name":"Andrew Wardley","route":"/people/andrew-wardley/"},{"id":"javier-cortes","kind":"person","name":"Javier Cortés","route":"/people/javier-cortes/"},{"id":"sohn-joohyuk","kind":"person","name":"Joohyuk Sohn","route":"/people/sohn-joohyuk/"},{"id":"miguel-martin","kind":"person","name":"Miguel Martín","route":"/people/miguel-martin/"},{"id":"sara-tolaney","kind":"person","name":"Sara M. Tolaney","route":"/people/sara-tolaney/"},{"id":"stephen-johnston","kind":"person","name":"Stephen Johnston","route":"/people/stephen-johnston/"},{"id":"shao-zhi-ming","kind":"person","name":"Zhi-Ming Shao","route":"/people/shao-zhi-ming/"}],"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-toxicity-qol","kind":"bottleneck","name":"Toxicity and quality of life are undervalued","route":"/bottlenecks/b-toxicity-qol/"}],"journal":[{"id":"jco","kind":"journal","name":"Journal of Clinical Oncology","route":"/journals/jco/"}]}}