{"entity":{"id":"oesophageal-adenocarcinoma","kind":"cancer","name":"Oesophageal and junctional adenocarcinoma","aka":["Esophageal adenocarcinoma","EAC","Gastro-oesophageal junction adenocarcinoma","Barrett's cancer"],"tldr":"Adenocarcinoma of the lower oesophagus and junction grows out of Barrett's oesophagus, the change in the lining caused by long-standing acid reflux. Chemotherapy or chemoradiation before surgery is standard, and HER2, PD-L1 and claudin 18.2 now guide drugs for advanced disease as they do in stomach cancer.","summary":"Oesophageal adenocarcinoma arises in the lower oesophagus and gastro-oesophageal junction from Barrett's oesophagus, driven by reflux, obesity and smoking; TP53 mutation, chromosomal instability and amplification of HER2, EGFR, MET or KRAS are typical. Barrett's surveillance and endoscopic ablation or resection of dysplasia prevent progression. Locally advanced disease is treated with perioperative FLOT chemotherapy, which the ESOPEC trial showed gives better survival than CROSS chemoradiation, followed by oesophagectomy. Advanced disease is managed with stomach cancer regimens: nivolumab or pembrolizumab with chemotherapy for PD-L1-positive tumours, trastuzumab with chemotherapy for HER2-positive tumours, zolbetuximab for claudin 18.2-positive tumours, and trastuzumab deruxtecan after HER2-directed therapy.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Esophageal_cancer","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Esophageal_cancer"}],"tags":["subtype-page"],"related":["oesophageal-squamous-cell-carcinoma"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["esopec","flot4"],"people":[],"bottlenecks":[],"keyPapers":["paper-checkmate-649-lancet-2021","paper-flot4-lancet-2019","paper-cross-nejm-2012","paper-keynote-590-lancet-2021"],"journals":[],"dependsOn":[],"notes":[],"group":"gastrointestinal","burden":"The dominant oesophageal cancer in Western countries, where its incidence has risen several-fold since the 1970s with reflux and obesity; it affects men six times more than women, and five-year survival is about 20 percent overall.","subtypes":["Barrett's-associated adenocarcinoma of the lower oesophagus","Gastro-oesophageal junction adenocarcinoma (Siewert types I to III)","HER2-positive (about 15 to 20 percent)","Claudin 18.2-positive","Mismatch repair-deficient (a minority)"],"biomarkers":["HER2 amplification","PD-L1 combined positive score","Claudin 18.2 expression","Mismatch repair and microsatellite instability","Barrett's dysplasia grade on surveillance"],"standardOfCare":[{"setting":"Barrett's oesophagus","approach":"Endoscopic surveillance; radiofrequency ablation or endoscopic resection for dysplasia and early cancer.","refs":["endoscopic-resection"]},{"setting":"Locally advanced","approach":"Perioperative FLOT (docetaxel, oxaliplatin, fluorouracil, leucovorin) and oesophagectomy, preferred over CROSS after ESOPEC; chemoradiation where chemotherapy is not tolerated.","refs":["flot","docetaxel","oxaliplatin","fluorouracil","cross"]},{"setting":"Advanced, first line","approach":"Nivolumab or pembrolizumab with platinum-fluoropyrimidine chemotherapy for PD-L1-positive tumours; trastuzumab with chemotherapy (and pembrolizumab) for HER2-positive tumours; zolbetuximab with chemotherapy for claudin 18.2-positive tumours.","refs":["nivolumab","pembrolizumab","trastuzumab","zolbetuximab","her2","pdl1","cldn18-2"]},{"setting":"Later lines","approach":"Trastuzumab deruxtecan for HER2-positive disease; ramucirumab with paclitaxel; trifluridine-tipiracil.","refs":["trastuzumab-deruxtecan","ramucirumab","paclitaxel"]}],"stateOfArt":["ESOPEC settled a decade-long argument in favour of perioperative chemotherapy over chemoradiation for adenocarcinoma.","Three biomarkers, HER2, PD-L1 and claudin 18.2, now decide first-line treatment of advanced disease.","Endoscopic therapy of Barrett's dysplasia prevents cancer and has replaced surgery for early disease."],"history":[{"year":1950,"title":"Norman Barrett describes the columnar-lined oesophagus","refs":[]},{"year":2010,"title":"ToGA: trastuzumab for HER2-positive gastro-oesophageal cancer","refs":["trastuzumab"]},{"year":2012,"title":"CROSS chemoradiation before surgery","refs":["cross"]},{"year":2019,"title":"FLOT4: perioperative FLOT beats ECF","refs":["flot"]},{"year":2024,"title":"ESOPEC: FLOT better than CROSS in adenocarcinoma","refs":["flot"]},{"year":2024,"title":"Zolbetuximab approved for claudin 18.2-positive disease","refs":["zolbetuximab"]}],"pipeline":["zolbetuximab","trastuzumab-deruxtecan"],"openProblems":["Barrett's surveillance finds few of the cancers that occur.","Rising incidence with obesity.","Oesophagectomy remains a major operation with lasting effects on eating."],"parent":"esophageal"},"route":"/cancers/oesophageal-adenocarcinoma/","neighbours":{"cancer":[{"id":"esophageal","kind":"cancer","name":"Oesophageal cancer","route":"/cancers/esophageal/"},{"id":"oesophageal-squamous-cell-carcinoma","kind":"cancer","name":"Oesophageal squamous cell carcinoma","route":"/cancers/oesophageal-squamous-cell-carcinoma/"}],"trial":[{"id":"nct07692204","kind":"trial","name":"A Dose Optimization/Expansion Study of SAR445877 in Adult Chinese Participants With Advanced Gastric or Gastroesophageal Junction Cancer","route":"/trials/nct07692204/"},{"id":"nct07069712","kind":"trial","name":"A Study of Novel Agents or Combinations as Perioperative Treatment in Participants With Locally Advanced Resectable Gastroesophageal Adenocarcinoma","route":"/trials/nct07069712/"},{"id":"nct06356311","kind":"trial","name":"A Study to Evaluate Sacituzumab Tirumotecan (MK-2870) in Advanced/Metastatic Gastroesophageal Adenocarcinoma (MK-2870-015)","route":"/trials/nct06356311/"},{"id":"nct05632939","kind":"trial","name":"ASKB589 in Combination With CAPOX and PD-1 Inhibitors in Patients With Advanced, and Unresectable G/GEJ Cancer.","route":"/trials/nct05632939/"},{"id":"checkmate-577","kind":"trial","name":"CheckMate 577","route":"/trials/checkmate-577/"},{"id":"nct02628665","kind":"trial","name":"Clinical Study of Time Optimizing of Endoscopic Photodynamic Therapy on Esophageal and/or Gastric Cardiac Cancer","route":"/trials/nct02628665/"},{"id":"cross","kind":"trial","name":"CROSS","route":"/trials/cross/"},{"id":"esopec","kind":"trial","name":"ESOPEC","route":"/trials/esopec/"},{"id":"flot4","kind":"trial","name":"FLOT4-AIO","route":"/trials/flot4/"},{"id":"keynote-590","kind":"trial","name":"KEYNOTE-590","route":"/trials/keynote-590/"},{"id":"nct03223662","kind":"trial","name":"Metabolomic and BH3 Profiling of Esophageal Cancers: Identification of Novel Assessment Methods of Treatment Response for Precision Therapy","route":"/trials/nct03223662/"},{"id":"nct07529808","kind":"trial","name":"Phase 1/2 Study of BHB810 in Advanced Gastric and GEJ Adenocarcinoma","route":"/trials/nct07529808/"},{"id":"nct07431281","kind":"trial","name":"Sonesitatug Vedotin in Combination With Capecitabine With or Without Rilvegostomig in Participants With Advanced or Metastatic Gastric, Gastroesophageal Junction, or Esophageal Adenocarcinoma Expressing Claudin18.2","route":"/trials/nct07431281/"},{"id":"nct06469944","kind":"trial","name":"Substudy 06C: A Study of Investigational Agents With Pembrolizumab (MK-3475) and Chemotherapy in Participants With First-Line Locally Advanced Unresectable/Metastatic Gastroesophageal Adenocarcinoma (MK-3475-06C/KEYMAKER-U06)","route":"/trials/nct06469944/"},{"id":"nct06445972","kind":"trial","name":"Substudy 06D: Combination Therapies in Second Line (2L) Gastroesophageal Adenocarcinoma (MK-3475-06D/Keymaker-U06)","route":"/trials/nct06445972/"},{"id":"symbiotic-gi-16","kind":"trial","name":"Symbiotic-GI-16: A Study to Learn About the Study Medicine Called PF-08634404 in Combination With Chemotherapy in Gastroesophageal Cancer","route":"/trials/symbiotic-gi-16/"}],"paper":[{"id":"paper-checkmate-649-lancet-2021","kind":"paper","name":"CheckMate 649: nivolumab plus chemotherapy as first treatment for advanced gastric, gastro-oesophageal junction and oesophageal adenocarcinoma","route":"/key-papers/paper-checkmate-649-lancet-2021/"},{"id":"paper-cross-nejm-2012","kind":"paper","name":"CROSS: preoperative chemoradiotherapy for oesophageal or junctional cancer","route":"/key-papers/paper-cross-nejm-2012/"},{"id":"paper-flot4-lancet-2019","kind":"paper","name":"FLOT4-AIO: perioperative FLOT versus ECF/ECX for resectable gastric or gastro-oesophageal junction adenocarcinoma","route":"/key-papers/paper-flot4-lancet-2019/"},{"id":"paper-keynote-590-lancet-2021","kind":"paper","name":"KEYNOTE-590: pembrolizumab plus chemotherapy for first-line treatment of advanced oesophageal cancer","route":"/key-papers/paper-keynote-590-lancet-2021/"}],"drug":[{"id":"docetaxel","kind":"drug","name":"Docetaxel","route":"/drugs/docetaxel/"},{"id":"flot","kind":"drug","name":"FLOT (5-FU, leucovorin, oxaliplatin, docetaxel)","route":"/drugs/flot/"},{"id":"fluorouracil","kind":"drug","name":"Fluorouracil (5-FU)","route":"/drugs/fluorouracil/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"oxaliplatin","kind":"drug","name":"Oxaliplatin","route":"/drugs/oxaliplatin/"},{"id":"paclitaxel","kind":"drug","name":"Paclitaxel / nab-paclitaxel","route":"/drugs/paclitaxel/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"ramucirumab","kind":"drug","name":"Ramucirumab","route":"/drugs/ramucirumab/"},{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"},{"id":"trastuzumab-deruxtecan","kind":"drug","name":"Trastuzumab deruxtecan","route":"/drugs/trastuzumab-deruxtecan/"},{"id":"zolbetuximab","kind":"drug","name":"Zolbetuximab","route":"/drugs/zolbetuximab/"}],"technology":[{"id":"ct-body-composition-sarcopenia","kind":"technology","name":"CT body composition and sarcopenia measurement","route":"/technologies/ct-body-composition-sarcopenia/"},{"id":"dpyd-genotyping","kind":"technology","name":"DPYD genotyping and DPD phenotyping before fluoropyrimidines","route":"/technologies/dpyd-genotyping/"},{"id":"endoscopic-resection","kind":"technology","name":"Endoscopic resection (EMR / ESD)","route":"/technologies/endoscopic-resection/"}],"target":[{"id":"axin1","kind":"target","name":"AXIN1","route":"/targets/axin1/"},{"id":"cant1","kind":"target","name":"CANT1","route":"/targets/cant1/"},{"id":"cdh11","kind":"target","name":"CDH11","route":"/targets/cdh11/"},{"id":"cdx2","kind":"target","name":"CDX2","route":"/targets/cdx2/"},{"id":"cldn18-2","kind":"target","name":"Claudin 18.2","route":"/targets/cldn18-2/"},{"id":"ctnnd2","kind":"target","name":"CTNND2","route":"/targets/ctnnd2/"},{"id":"dcc","kind":"target","name":"DCC","route":"/targets/dcc/"},{"id":"epha3","kind":"target","name":"EPHA3","route":"/targets/epha3/"},{"id":"grm3","kind":"target","name":"GRM3","route":"/targets/grm3/"},{"id":"h3c2","kind":"target","name":"H3C2","route":"/targets/h3c2/"},{"id":"her2","kind":"target","name":"HER2","route":"/targets/her2/"},{"id":"hla-b","kind":"target","name":"HLA-B","route":"/targets/hla-b/"},{"id":"kat6a","kind":"target","name":"KAT6A","route":"/targets/kat6a/"},{"id":"msn","kind":"target","name":"MSN","route":"/targets/msn/"},{"id":"nbea","kind":"target","name":"NBEA","route":"/targets/nbea/"},{"id":"ncoa2","kind":"target","name":"NCOA2","route":"/targets/ncoa2/"},{"id":"numa1","kind":"target","name":"NUMA1","route":"/targets/numa1/"},{"id":"nutm1","kind":"target","name":"NUTM1","route":"/targets/nutm1/"},{"id":"pdl1","kind":"target","name":"PD-L1","route":"/targets/pdl1/"},{"id":"tgfbr1","kind":"target","name":"TGFBR1","route":"/targets/tgfbr1/"},{"id":"znf208","kind":"target","name":"ZNF208","route":"/targets/znf208/"},{"id":"znf750","kind":"target","name":"ZNF750","route":"/targets/znf750/"}],"person":[{"id":"jens-hoeppner","kind":"person","name":"Jens Höppner","route":"/people/jens-hoeppner/"},{"id":"jong-mu-sun","kind":"person","name":"Jong-Mu Sun","route":"/people/jong-mu-sun/"},{"id":"salah-eddin-al-batran","kind":"person","name":"Salah-Eddin Al-Batran","route":"/people/salah-eddin-al-batran/"}],"company":[{"id":"aio","kind":"company","name":"AIO (Arbeitsgemeinschaft Internistische Onkologie)","route":"/companies/aio/"}]}}