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9 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
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.
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.
The 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.
| Setting | Approach | Guideline |
|---|---|---|
| First line, mismatch-repair proficient | CAPOX or FOLFOX, with bevacizumab considered; taxane-based regimens as an alternative. | not mapped |
| First line, mismatch-repair deficient | Pembrolizumab (tumour-agnostic approval); nivolumab with ipilimumab as an alternative. | not mapped |
| Second line | FOLFIRI or a taxane; pembrolizumab if mismatch-repair deficient and not yet given; trastuzumab-based therapy or trastuzumab deruxtecan for HER2-positive tumours. | not mapped |
| Limited metastases | Resection of liver metastases or cytoreductive surgery with HIPEC for limited peritoneal disease in selected patients. | not mapped |
| All patients | Comprehensive genomic profiling to find HER2, mismatch repair deficiency and rare actionable alterations; referral to trials. | not mapped |