{"entity":{"id":"oral-serd-plus-cdk46-after-esr1","kind":"pairing","name":"Oral SERD + CDK4/6 inhibitor after ESR1 emergence","aka":[],"tldr":"When an ESR1 mutation appears, swap the aromatase inhibitor for an oral SERD and keep the CDK4/6 inhibitor going.","summary":"This sequence swaps the aromatase inhibitor for the oral SERD camizestrant when an ESR1 mutation emerges in HR-positive, HER2-negative breast cancer, while the CDK4/6 inhibitor continues. ESR1 mutations make the oestrogen receptor ligand-independent, which neutralises aromatase inhibitors but not degraders, and the tumour's dependence on CDK4/6 persists. SERENA-6 tested the switch at the moment ESR1 appeared in ctDNA, and EMBER-3 paired imlunestrant with abemaciclib; both phase 3 trials were positive for progression-free survival, and camizestrant received FDA accelerated approval in 2026. Replacing the aromatase inhibitor up front without molecular selection, as in persevERA, failed, so the timing of the switch is the point.","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT04964934: SERENA-6","url":"https://clinicaltrials.gov/study/NCT04964934"},{"label":"ClinicalTrials.gov NCT04975308: EMBER-3","url":"https://clinicaltrials.gov/study/NCT04975308"}],"tags":[],"related":[],"cancers":["breast-hr-positive"],"sections":[],"technologies":[],"targets":[],"drugs":["camizestrant","imlunestrant","abemaciclib"],"companies":[],"institutions":[],"pathways":[],"terms":["esr1-mutation"],"trials":["serena-6","ember-3"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"a":"camizestrant","b":"cdk46-inhibitor","rationale":"ESR1 mutations make ER ligand-independent, neutralising AIs but not degraders; CDK4/6 dependence persists.","evidence":"Two positive phase 3 trials; FDA accelerated approval (camizestrant) 2026.","pairingType":"sequence"},"route":"/pairings/oral-serd-plus-cdk46-after-esr1/","neighbours":{"cancer":[{"id":"breast-hr-positive","kind":"cancer","name":"HR-positive / HER2-negative breast cancer","route":"/cancers/breast-hr-positive/"}],"drug":[{"id":"abemaciclib","kind":"drug","name":"Abemaciclib","route":"/drugs/abemaciclib/"},{"id":"camizestrant","kind":"drug","name":"Camizestrant","route":"/drugs/camizestrant/"},{"id":"imlunestrant","kind":"drug","name":"Imlunestrant","route":"/drugs/imlunestrant/"}],"term":[{"id":"esr1-mutation","kind":"term","name":"ESR1 mutation","route":"/terms/esr1-mutation/"}],"trial":[{"id":"ember-3","kind":"trial","name":"EMBER-3","route":"/trials/ember-3/"},{"id":"serena-6","kind":"trial","name":"SERENA-6","route":"/trials/serena-6/"}],"technology":[{"id":"cdk46-inhibitor","kind":"technology","name":"CDK4/6 inhibitors","route":"/technologies/cdk46-inhibitor/"}]}}