Treatment of locally advanced or metastatic ampullary carcinoma with proficient mismatch repair (pMMR)

This protocol applies to patients with locally advanced or metastatic ampullary adenocarcinoma whose tumours show proficient mismatch repair (pMMR) status and belong to the pancreatobiliary (PB) or mixed (MT) histological subtype, with an ECOG performance status of 2 or less.

Clinical scenario

Disease is locally advanced or metastatic and not amenable to curative surgery. Mismatch repair testing confirms proficient (pMMR) status, distinguishing this population from dMMR/MSI-H patients. Histological subtype is pancreatobiliary (PB) or mixed (MT), and the patient’s performance status supports active treatment.

Treatment approach

Chemotherapy in this setting is guided by the patient’s general condition, histological subtype, and the results of molecular biomarker testing. The choice of regimen is shaped by specific actionable findings — the full decision algorithm, including all relevant options and their evidence grading, is available in the complete protocol.

Instant Access to Structured Evidence-Based Regimens

References

DOI: 10.1016/j.dld.2024.04.027

For pMMR AC, first line chemotherapy may be adapted according to general condition, and INT / PB / MT subtype.
For dMMR/MSI-H AC: when not used in first line, ICI is a valid option (grade C).
For Her2 positive AC: FOLFOX or 5FU and antiHer2 therapy (expert agreement).
For FGFR2 translocation: FGFR2 inhibitors (expert agreement).
For AC harboring NTRK fusions: larotrectinib or entrectinib (expert agreement).
Irinotecan based: FOLFIRI (expert opinion).
Gemcitabine based (expert opinion).
Taxane based (expert opinion) if contraindication for oxaliplatin.

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