{"entity":{"id":"monarch-3","kind":"trial","name":"MONARCH 3","aka":[],"tldr":"Abemaciclib roughly doubled the time to progression when added to an aromatase inhibitor; the survival gain of about 13 months narrowly missed statistical significance.","summary":"MONARCH 3, trial NCT02246621 sponsored by Eli Lilly and reported in 2017, showed that abemaciclib roughly doubled the time to progression when added to a non-steroidal aromatase inhibitor as first-line treatment for postmenopausal HR-positive, HER2-negative advanced breast cancer. It randomised 493 women and met its primary progression-free survival endpoint, and the final overall survival analysis showed a numerical gain of about thirteen months that narrowly missed statistical significance at the prespecified threshold. OnCo links it to CDK4/6 as a target, abemaciclib, aromatase inhibitors, Matthew P. Goetz and the bottleneck of wrong doses, and MONARCH 2, which tested abemaciclib with fulvestrant after endocrine progression, did show a significant survival benefit. Whether a large numerical survival gain that misses significance should count is the question the trial leaves open.","status":"positive","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT02246621","url":"https://clinicaltrials.gov/study/NCT02246621"}],"tags":[],"related":[],"cancers":["breast-hr-positive"],"sections":[],"technologies":["cdk46-inhibitor"],"targets":["cdk4-6"],"drugs":["abemaciclib"],"companies":["eli-lilly"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["matthew-goetz"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT02246621","phase":"3","setting":"First-line postmenopausal HR+/HER2- advanced breast cancer: abemaciclib + NSAI vs placebo + NSAI","sponsor":"Eli Lilly","result":"PFS HR 0.54; OS 66.8 vs 53.7 months, HR 0.80 (NS).","started":"2014-11-06","startedType":"actual","yearReported":2017,"enrolled":493,"enrolledBasis":"registry","outcomes":[{"endpoint":"Progression-free survival","primary":true,"unit":"months","arms":[{"name":"Abemaciclib + NSAI","n":328,"value":28.2},{"name":"Placebo + NSAI","n":165,"value":14.8}],"hr":0.54,"ci":[0.42,0.7],"source":"https://ascopubs.org/doi/10.1200/JCO.2017.75.6155"},{"endpoint":"Overall survival","unit":"months","arms":[{"name":"Abemaciclib + NSAI","value":66.8},{"name":"Placebo + NSAI","value":53.7}],"hr":0.8,"ci":[0.62,1.03],"p":"0.066","source":"https://doi.org/10.1200/JCO.2017.75.6155"}],"replication":"MONARCH 2 (abemaciclib + fulvestrant after endocrine progression) did show a significant OS benefit (HR 0.76)."},"route":"/trials/monarch-3/","neighbours":{"cancer":[{"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/"}],"target":[{"id":"cdk4-6","kind":"target","name":"CDK4/6","route":"/targets/cdk4-6/"}],"drug":[{"id":"abemaciclib","kind":"drug","name":"Abemaciclib","route":"/drugs/abemaciclib/"},{"id":"letrozole","kind":"drug","name":"Letrozole (and other aromatase inhibitors)","route":"/drugs/letrozole/"}],"company":[{"id":"eli-lilly","kind":"company","name":"Eli Lilly (incl. Loxo)","route":"/companies/eli-lilly/"}],"person":[{"id":"matthew-goetz","kind":"person","name":"Matthew P. Goetz","route":"/people/matthew-goetz/"}],"bottleneck":[{"id":"b-dose-optimisation","kind":"bottleneck","name":"Wrong doses","route":"/bottlenecks/b-dose-optimisation/"}],"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/"}]}}