Treatment of Metastatic Colon Cancer with dMMR/MSI-H or POLE/POLD1 Ultra-Hypermutated Phenotype
Clinical Scenario
This protocol applies to patients with metastatic colon adenocarcinoma (any T, any N, M1) — including suspected or proven synchronous metastatic disease — whose tumour carries a mismatch repair deficient (dMMR) or MSI-high (MSI-H) profile, or a POLE/POLD1 mutation producing an ultra-hypermutated phenotype (e.g., tumour mutational burden >50 mut/Mb).
dMMR / MSI-H
POLE / POLD1 mutation
TMB >50 mut/Mb
Metastatic adenocarcinoma
Approach Overview
For this molecularly defined subgroup, the management approach involves immunotherapy-based systemic therapy. Option selection is informed by prior treatment history — in particular, whether checkpoint inhibitor therapy has been administered previously. The full regimen criteria, decision algorithm, and sequencing details are contained in the structured protocol.
References
- dMMR/MSI-H or POLE/POLD1 mutation with ultra-hypermutated phenotype (eg, TMB >50 mut/Mb)
- Suspected or proven metastatic synchronous adenocarcinoma (any T, any N, M1)
- Systemic therapy (see COL-D)
- Ipilimumab + Nivolumab (if checkpoint inhibitor monotherapy was previously received)