Treatment of Metastatic Colon Cancer with dMMR/MSI-H or POLE/POLD1 Ultra-Hypermutated Phenotype
This protocol addresses metastatic colon adenocarcinoma (any T, any N, M1) in patients whose tumours carry mismatch-repair deficiency (dMMR), microsatellite instability-high (MSI-H) status, or a POLE/POLD1 mutation associated with an ultra-hypermutated phenotype — defined, for example, by a tumour mutational burden above 50 mut/Mb.
The defining molecular feature is deficient mismatch-repair or extreme hypermutation driven by POLE/POLD1 mutations (e.g., TMB > 50 mut/Mb). This tumour biology distinguishes this population from microsatellite-stable metastatic colon cancer and has direct implications for the treatment approach.
Checkpoint inhibitor immunotherapy is the indicated systemic strategy for this molecular subtype and may be used across any line of therapy in patients who have not previously received immunotherapy — multiple agents across the PD-1, PD-L1, and PD-1/CTLA-4 axes are included in the structured regimen options.
- 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)
- Checkpoint Inhibitor Therapy for Any Line of Therapy