{"entity":{"id":"serena-6","kind":"trial","name":"SERENA-6","aka":[],"tldr":"The first trial to change treatment because of a blood test rather than a scan: switching to camizestrant when an ESR1 mutation appeared in the blood delayed progression by seven months.","summary":"3,256 patients screened by serial ctDNA; 315 with an emergent ESR1 mutation randomised. PFS 16.0 vs 9.2 months (HR 0.44, P<0.0001). OS immature; no crossover. FDA ODAC voted 6-3 against (30 April 2026), questioning the clinical meaning of acting on ctDNA before progression; the FDA nonetheless granted accelerated approval on 4 September 2026 (Etcamah), the first ctDNA-triggered switch indication.","status":"positive","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT04964934","url":"https://clinicaltrials.gov/study/NCT04964934"},{"label":"ASCO Post approval","url":"https://ascopost.com/news/september-2026/fda-approves-camizestrant-combination-regimen-for-locally-advanced-or-metastatic-breast-cancer/"},{"label":"ODAC vote (CancerNetwork)","url":"https://www.cancernetwork.com/view/fda-odac-no-camizestrant-for-hr-her2-esr1-advanced-breast-cancer"}],"tags":[],"related":["src-asco-post","src-cancer-network"],"cancers":["breast-hr-positive","hr-positive-metastatic-post-cdk46"],"sections":[],"technologies":["liquid-biopsy"],"targets":["estrogen-receptor"],"drugs":["camizestrant"],"companies":["astrazeneca"],"institutions":[],"pathways":[],"terms":["esr1-mutation","ctdna"],"trials":[],"people":["nicholas-turner"],"bottlenecks":[],"keyPapers":["paper-serena-6-n-engl-j-med-2025"],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT04964934","phase":"3","setting":"First-line HR+/HER2- advanced breast cancer on AI + CDK4/6 with an ESR1 mutation detected in ctDNA before radiographic progression: switch to camizestrant + CDK4/6 vs continue AI + CDK4/6","sponsor":"AstraZeneca","result":"PFS 16.0 vs 9.2 months, HR 0.44.","started":"2021-06-30","startedType":"actual","yearReported":2025,"enrolled":315,"enrolledBasis":"registry","outcomes":[{"endpoint":"Progression-free survival","primary":true,"unit":"months","arms":[{"name":"Switch to camizestrant + CDK4/6","n":157,"value":16},{"name":"Continue AI + CDK4/6","n":158,"value":9.2}],"hr":0.44,"ci":[0.31,0.6],"p":"<0.0001","source":"https://www.onclive.com/view/fda-approves-camizestrant-plus-a-cdk4-6-inhibitor-for-emergent-esr1-mutated-hr-her2-advanced-breast-cancer"}],"replication":"Single trial; the strategy (ctDNA-triggered switch) has not been replicated with another agent. OS pending."},"route":"/trials/serena-6/","neighbours":{"collection":[{"id":"src-cancer-network","kind":"collection","name":"CancerNetwork (ONCOLOGY)","route":"/collections/src-cancer-network/"},{"id":"src-asco-post","kind":"collection","name":"The ASCO Post","route":"/collections/src-asco-post/"}],"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":"liquid-biopsy","kind":"technology","name":"Liquid biopsy (ctDNA)","route":"/technologies/liquid-biopsy/"}],"target":[{"id":"estrogen-receptor","kind":"target","name":"Estrogen receptor (ERα)","route":"/targets/estrogen-receptor/"}],"drug":[{"id":"camizestrant","kind":"drug","name":"Camizestrant","route":"/drugs/camizestrant/"}],"company":[{"id":"astrazeneca","kind":"company","name":"AstraZeneca","route":"/companies/astrazeneca/"}],"term":[{"id":"ctdna","kind":"term","name":"Circulating tumour DNA (ctDNA)","route":"/terms/ctdna/"},{"id":"esr1-mutation","kind":"term","name":"ESR1 mutation","route":"/terms/esr1-mutation/"},{"id":"odac","kind":"term","name":"ODAC (Oncologic Drugs Advisory Committee)","route":"/terms/odac/"},{"id":"progressive-disease","kind":"term","name":"Progressive disease and radiographic progression","route":"/terms/progressive-disease/"},{"id":"serd","kind":"term","name":"Selective oestrogen receptor degrader (SERD)","route":"/terms/serd/"}],"person":[{"id":"nicholas-turner","kind":"person","name":"Nicholas Turner","route":"/people/nicholas-turner/"}],"paper":[{"id":"paper-serena-6-n-engl-j-med-2025","kind":"paper","name":"First-Line Camizestrant for Emerging ESR1 -Mutated Advanced Breast Cancer","route":"/key-papers/paper-serena-6-n-engl-j-med-2025/"}],"pairing":[{"id":"oral-serd-plus-cdk46-after-esr1","kind":"pairing","name":"Oral SERD + CDK4/6 inhibitor after ESR1 emergence","route":"/pairings/oral-serd-plus-cdk46-after-esr1/"}],"idea":[{"id":"idea-ctdna-switch-generalised","kind":"idea","name":"Molecular-progression switching beyond ESR1","route":"/ideas/idea-ctdna-switch-generalised/"}],"bottleneck":[{"id":"b-resistance","kind":"bottleneck","name":"Acquired resistance to every therapy","route":"/bottlenecks/b-resistance/"},{"id":"b-tumor-heterogeneity","kind":"bottleneck","name":"Tumour heterogeneity and clonal evolution","route":"/bottlenecks/b-tumor-heterogeneity/"}],"roadmap":[{"id":"diagnostics-roadmap","kind":"roadmap","name":"Diagnostics roadmap: stains → gene panels → blood tests that decide treatment","route":"/roadmaps/diagnostics-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/"},{"id":"targeted-therapy-roadmap","kind":"roadmap","name":"Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall","route":"/roadmaps/targeted-therapy-roadmap/"},{"id":"trial-modernisation-roadmap","kind":"roadmap","name":"Trial modernisation roadmap: the randomised trial → platforms and adaptive designs → decentralised, pragmatic and always-on","route":"/roadmaps/trial-modernisation-roadmap/"}]}}