{"entity":{"id":"advanced-small-bowel-adenocarcinoma","kind":"cancer","name":"Advanced and metastatic small bowel adenocarcinoma","aka":["Metastatic small bowel adenocarcinoma","Stage IV SBA","Unresectable small intestine adenocarcinoma","Recurrent small bowel adenocarcinoma"],"tldr":"Advanced small bowel adenocarcinoma is cancer of the small intestine that has spread to the liver, peritoneum or elsewhere, treated with the chemotherapy used for bowel cancer, oxaliplatin with a fluoropyrimidine, then taxanes or irinotecan. The exception is the sizeable minority with mismatch-repair-deficient tumours, for whom the immunotherapy pembrolizumab works far better than chemotherapy.","summary":"Metastatic small bowel adenocarcinoma has been treated for two decades with regimens borrowed from colorectal cancer, guided by phase 2 trials rather than randomised evidence. Capecitabine with oxaliplatin (CAPOX) produced responses in about half of patients in a phase 2 trial at MD Anderson (Journal of Clinical Oncology 2009) and, with FOLFOX, became the first-line standard; FOLFIRI is used in second line, and a randomised Japanese phase 2 and a French cohort supported these choices. Bevacizumab is added by analogy with colon cancer, while anti-EGFR antibodies are not used because the tumours behave more like gastric than colorectal cancer in that respect and are usually KRAS mutant or otherwise unresponsive. In the BALLAD era, the NCCN guideline lists taxane-based regimens as a further option, reflecting the tumour's kinship with gastric adenocarcinoma.\n\nThe molecular exceptions matter more than in colon cancer. Mismatch repair deficiency, found in a larger proportion of small bowel than colorectal adenocarcinomas, predicts benefit from pembrolizumab, approved for all mismatch-repair-deficient solid tumours in 2017 and recommended in first line for these patients; the ZEBRA phase 2 trial of pembrolizumab in unselected small bowel adenocarcinoma found responses concentrated in the mismatch-repair-deficient minority. HER2 amplification or mutation occurs in a subset and responds to trastuzumab-based therapy or trastuzumab deruxtecan in tumour-agnostic trials, and comprehensive genomic profiling is recommended for every patient with advanced disease. Resection of limited liver or peritoneal metastases and cytoreductive surgery with HIPEC are considered in selected patients, and circulating tumour DNA is being explored for monitoring. Survival remains shorter than in colorectal cancer, in part because the tumours respond less and in part because they are diagnosed late.","asOf":"2026-09-18","wikipedia":"https://en.wikipedia.org/wiki/Small_intestine_cancer","links":[{"label":"CAPOX phase 2 in small bowel adenocarcinoma (JCO 2009)","url":"https://doi.org/10.1200/JCO.2008.19.7145"},{"label":"NCCN Small Bowel Adenocarcinoma","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1490"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Small_intestine_cancer"}],"tags":["subtype-page","gastrointestinal"],"related":["localised-small-bowel-adenocarcinoma","small-bowel","colorectal","msi-high-colorectal"],"cancers":[],"sections":[],"technologies":["cytotoxic-chemotherapy","checkpoint-inhibitor","cgp","hipec"],"targets":["her2","kras","pd1"],"drugs":["capox","folfox","folfiri","bevacizumab","paclitaxel","pembrolizumab","nivolumab","trastuzumab-deruxtecan"],"companies":[],"institutions":[],"pathways":[],"terms":["msi","tumour-agnostic","peritoneal-metastasis"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-overman-capox-small-bowel-adenocarcinoma-jco-2009","paper-zebra-pembrolizumab-small-bowel-adenocarcinoma-ccr-2021"],"journals":[],"dependsOn":[],"notes":[],"group":"gastrointestinal","burden":"About a third of patients present with metastases, to the liver, peritoneum and distant nodes, and many more relapse after surgery; survival is shorter than in colorectal cancer stage for stage.","subtypes":["Synchronous metastatic small bowel adenocarcinoma (liver, peritoneum, distant nodes)","Recurrent small bowel adenocarcinoma after resection","Mismatch-repair-deficient advanced small bowel adenocarcinoma (pembrolizumab first line)","HER2-positive advanced small bowel adenocarcinoma (HER2-directed therapy)","Peritoneal metastases from small bowel adenocarcinoma (cytoreduction and HIPEC in selected patients)","Duodenal versus jejunoileal advanced adenocarcinoma"],"biomarkers":["Mismatch repair and microsatellite status (pembrolizumab)","HER2 amplification or ERBB2 mutation (HER2-directed therapy)","KRAS, BRAF and other alterations on comprehensive genomic profiling","Tumour mutational burden","CEA and CA 19-9 for monitoring","Circulating tumour DNA (investigational)"],"standardOfCare":[{"setting":"First line, mismatch-repair proficient","approach":"CAPOX or FOLFOX, with bevacizumab considered; taxane-based regimens as an alternative.","refs":["capox","folfox","bevacizumab","paclitaxel","cytotoxic-chemotherapy"],"guideline":{"version":"NCCN Guidelines: Small Bowel Adenocarcinoma","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1490"}},{"setting":"First line, mismatch-repair deficient","approach":"Pembrolizumab (tumour-agnostic approval); nivolumab with ipilimumab as an alternative.","refs":["pembrolizumab","nivolumab","msi","mismatch-repair-msi","checkpoint-inhibitor"],"guideline":{"version":"NCCN Guidelines: Small Bowel Adenocarcinoma","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1490"}},{"setting":"Second line","approach":"FOLFIRI or a taxane; pembrolizumab if mismatch-repair deficient and not yet given; trastuzumab-based therapy or trastuzumab deruxtecan for HER2-positive tumours.","refs":["folfiri","paclitaxel","pembrolizumab","trastuzumab-deruxtecan"],"guideline":{"version":"NCCN Guidelines: Small Bowel Adenocarcinoma","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1490"}},{"setting":"Limited metastases","approach":"Resection of liver metastases or cytoreductive surgery with HIPEC for limited peritoneal disease in selected patients.","refs":["hepatectomy","hipec","peritoneal-metastasis"],"guideline":{"version":"NCCN Guidelines: Small Bowel Adenocarcinoma","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1490"}},{"setting":"All patients","approach":"Comprehensive genomic profiling to find HER2, mismatch repair deficiency and rare actionable alterations; referral to trials.","refs":["cgp","tumour-agnostic"],"guideline":{"version":"NCCN Guidelines: Small Bowel Adenocarcinoma","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1490"}}],"stateOfArt":["Oxaliplatin-fluoropyrimidine doublets remain first line on phase 2 evidence.","Pembrolizumab transforms outcomes for the mismatch-repair-deficient minority.","Genomic profiling finds HER2 and other targets in a further subset."],"history":[{"year":2009,"title":"CAPOX phase 2 establishes oxaliplatin-fluoropyrimidine as first-line therapy","refs":["capox"]},{"year":2017,"title":"Pembrolizumab approved for mismatch-repair-deficient solid tumours including small bowel adenocarcinoma","refs":["pembrolizumab","msi"]},{"year":2021,"title":"ZEBRA: pembrolizumab responses in unselected small bowel adenocarcinoma confined largely to mismatch-repair-deficient tumours","refs":["pembrolizumab"]},{"year":2024,"title":"Trastuzumab deruxtecan receives tumour-agnostic approval for HER2-positive solid tumours","refs":["trastuzumab-deruxtecan"]}],"pipeline":["pembrolizumab","trastuzumab-deruxtecan","signatera"],"openProblems":["No randomised phase 3 trial has ever been completed in advanced small bowel adenocarcinoma.","Mismatch-repair-proficient tumours have no effective immunotherapy.","Anti-EGFR and other colorectal targeted drugs do not translate.","Rarity makes trials slow and most evidence is retrospective."],"parent":"small-bowel"},"route":"/cancers/advanced-small-bowel-adenocarcinoma/","neighbours":{"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"localised-small-bowel-adenocarcinoma","kind":"cancer","name":"Localised small bowel adenocarcinoma (stage I to III, resected)","route":"/cancers/localised-small-bowel-adenocarcinoma/"},{"id":"msi-high-colorectal","kind":"cancer","name":"Mismatch-repair deficient (MSI-high) colorectal cancer","route":"/cancers/msi-high-colorectal/"},{"id":"small-bowel","kind":"cancer","name":"Small intestine cancer (small bowel adenocarcinoma)","route":"/cancers/small-bowel/"}],"technology":[{"id":"cgp","kind":"technology","name":"Comprehensive genomic profiling","route":"/technologies/cgp/"},{"id":"cytotoxic-chemotherapy","kind":"technology","name":"Cytotoxic chemotherapy","route":"/technologies/cytotoxic-chemotherapy/"},{"id":"hipec","kind":"technology","name":"HIPEC / PIPAC (intraperitoneal chemotherapy)","route":"/technologies/hipec/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}],"target":[{"id":"her2","kind":"target","name":"HER2","route":"/targets/her2/"},{"id":"kras","kind":"target","name":"KRAS","route":"/targets/kras/"},{"id":"pd1","kind":"target","name":"PD-1","route":"/targets/pd1/"}],"drug":[{"id":"bevacizumab","kind":"drug","name":"Bevacizumab","route":"/drugs/bevacizumab/"},{"id":"capox","kind":"drug","name":"CAPOX (capecitabine, oxaliplatin)","route":"/drugs/capox/"},{"id":"folfiri","kind":"drug","name":"FOLFIRI (5-FU, leucovorin, irinotecan)","route":"/drugs/folfiri/"},{"id":"folfox","kind":"drug","name":"FOLFOX (5-FU, leucovorin, oxaliplatin)","route":"/drugs/folfox/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"paclitaxel","kind":"drug","name":"Paclitaxel / nab-paclitaxel","route":"/drugs/paclitaxel/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"signatera","kind":"drug","name":"Signatera","route":"/drugs/signatera/"},{"id":"trastuzumab-deruxtecan","kind":"drug","name":"Trastuzumab deruxtecan","route":"/drugs/trastuzumab-deruxtecan/"}],"term":[{"id":"hepatectomy","kind":"term","name":"Hepatectomy (liver resection)","route":"/terms/hepatectomy/"},{"id":"msi","kind":"term","name":"Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR)","route":"/terms/msi/"},{"id":"peritoneal-metastasis","kind":"term","name":"Peritoneal metastasis","route":"/terms/peritoneal-metastasis/"},{"id":"tumour-agnostic","kind":"term","name":"Tumour-agnostic (tissue-agnostic) approval","route":"/terms/tumour-agnostic/"}],"paper":[{"id":"paper-overman-capox-small-bowel-adenocarcinoma-jco-2009","kind":"paper","name":"Phase 2 study of capecitabine and oxaliplatin for advanced adenocarcinoma of the small bowel and ampulla of Vater","route":"/key-papers/paper-overman-capox-small-bowel-adenocarcinoma-jco-2009/"},{"id":"paper-zebra-pembrolizumab-small-bowel-adenocarcinoma-ccr-2021","kind":"paper","name":"ZEBRA: pembrolizumab in advanced small bowel adenocarcinoma","route":"/key-papers/paper-zebra-pembrolizumab-small-bowel-adenocarcinoma-ccr-2021/"}],"pathway":[{"id":"mismatch-repair-msi","kind":"pathway","name":"Mismatch repair & microsatellite instability","route":"/pathways/mismatch-repair-msi/"}]}}