Treatment of Locally Advanced or Metastatic Ampullary Adenocarcinoma with Deficient Mismatch Repair (dMMR) / MSI-High

Patients with locally advanced or metastatic ampullary carcinoma whose tumours carry deficient mismatch repair (dMMR) or microsatellite instability–high (MSI-H) status — and who have an ECOG performance status of 0–1 — represent a distinct clinical population with specific first-line treatment considerations separate from mismatch-repair–proficient disease.

Clinical Scenario

Locally advanced or metastatic ampullary carcinoma with confirmed dMMR / MSI-high tumour biology and ECOG performance status 0–1. This molecular profile, more frequently observed in the intestinal subtype of ampullary carcinoma, defines a population for whom a distinct first-line therapeutic approach is recommended.

First-Line Treatment Approach

For dMMR / MSI-high ampullary carcinoma, immune checkpoint inhibition is the preferred first-line option. A cytotoxic systemic approach represents the best alternative when immunotherapy is not selected.

Full regimen details — including agent selection, sequencing, and dosing — are available in the complete structured protocol.

Instant Access to Structured Evidence-Based Regimens

References

DOI: 10.1016/j.dld.2024.04.027

For dMMR AC, ICI may be the preferred option (grade C). Cytotoxic chemotherapy (the same as for pMMR AC) is the best other option (expert opinion).
For dMMR/MSI-high AC, more common in the INT subtype of AC, ICI might be the preferred first line treatment as for treatment of dMMR metastatic colorectal carcinomas, though no randomized study support this proposition.

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