{"entity":{"id":"emerald","kind":"trial","name":"EMERALD","aka":[],"tldr":"The first oral oestrogen-receptor degrader to beat standard hormone therapy, with the benefit concentrated in tumours carrying ESR1 mutations.","summary":"EMERALD, trial NCT03778931 sponsored by Radius and Menarini and reported in 2021, was the first trial in which an oral oestrogen receptor degrader beat standard hormone therapy, with the benefit concentrated in tumours carrying ESR1 mutations. It randomised 478 women with ER-positive, HER2-negative advanced breast cancer after one or two endocrine lines including a CDK4/6 inhibitor to elacestrant or standard endocrine therapy, met its primary progression-free survival endpoints in the whole population and the ESR1-mutant group, with a larger effect in the mutant group that grew with longer prior CDK4/6 exposure, and led to approval in January 2023 for ESR1-mutant disease with a ctDNA companion diagnostic. The ESR1-restricted benefit was replicated by EMBER-3 and VERITAC-2, and whether oral SERDs help without the mutation remains open.","status":"positive","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT03778931","url":"https://clinicaltrials.gov/study/NCT03778931"}],"tags":[],"related":[],"cancers":["breast-hr-positive","hr-positive-metastatic-post-cdk46"],"sections":[],"technologies":["endocrine-therapy"],"targets":["estrogen-receptor"],"drugs":["elacestrant"],"companies":[],"institutions":[],"pathways":[],"terms":["esr1-mutation"],"trials":[],"people":["francois-clement-bidard","aditya-bardia"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT03778931","phase":"3","setting":"ER+/HER2- advanced breast cancer after 1-2 endocrine lines including a CDK4/6 inhibitor: elacestrant vs standard endocrine therapy","sponsor":"Radius / Menarini","result":"PFS HR 0.55 in ESR1-mutant.","started":"2019-05-10","startedType":"actual","yearReported":2021,"enrolled":478,"enrolledBasis":"registry","outcomes":[{"endpoint":"Progression-free survival (ESR1-mutant)","primary":true,"unit":"months","arms":[{"name":"Elacestrant","n":115,"value":3.8},{"name":"Standard endocrine therapy","n":113,"value":1.9}],"hr":0.55,"ci":[0.39,0.77],"p":"0.0005","source":"https://ascopubs.org/doi/10.1200/JCO.22.00338"},{"endpoint":"Progression-free survival (all patients)","primary":true,"unit":"months","arms":[{"name":"Elacestrant","n":239,"value":2.8},{"name":"Standard endocrine therapy","n":239,"value":1.9}],"hr":0.7,"ci":[0.55,0.88],"p":"0.002","source":"https://doi.org/10.1200/JCO.22.00338"}],"replication":"The ESR1-mutant-restricted benefit was replicated by imlunestrant (EMBER-3) and vepdegestrant (VERITAC-2)."},"route":"/trials/emerald/","neighbours":{"cancer":[{"id":"breast-hr-positive","kind":"cancer","name":"HR-positive / HER2-negative breast cancer","route":"/cancers/breast-hr-positive/"},{"id":"hr-positive-metastatic-post-cdk46","kind":"cancer","name":"HR-positive metastatic breast cancer after CDK4/6 inhibitors","route":"/cancers/hr-positive-metastatic-post-cdk46/"}],"technology":[{"id":"endocrine-therapy","kind":"technology","name":"Endocrine therapy (SERMs, AIs, SERDs)","route":"/technologies/endocrine-therapy/"}],"target":[{"id":"estrogen-receptor","kind":"target","name":"Estrogen receptor (ERα)","route":"/targets/estrogen-receptor/"}],"drug":[{"id":"elacestrant","kind":"drug","name":"Elacestrant","route":"/drugs/elacestrant/"}],"term":[{"id":"esr1-mutation","kind":"term","name":"ESR1 mutation","route":"/terms/esr1-mutation/"},{"id":"serd","kind":"term","name":"Selective oestrogen receptor degrader (SERD)","route":"/terms/serd/"}],"person":[{"id":"aditya-bardia","kind":"person","name":"Aditya Bardia","route":"/people/aditya-bardia/"},{"id":"francois-clement-bidard","kind":"person","name":"François-Clément Bidard","route":"/people/francois-clement-bidard/"}],"paper":[{"id":"paper-emerald-elacestrant-jco-2022","kind":"paper","name":"EMERALD: elacestrant versus standard endocrine therapy after a CDK4/6 inhibitor","route":"/key-papers/paper-emerald-elacestrant-jco-2022/"}],"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/"}]}}