This protocol covers metastatic colon adenocarcinoma in patients whose tumours are proficient mismatch repair (pMMR) / microsatellite stable (MSS) and harbour a KRAS or NRAS mutation alongside BRAF wild-type status — a molecular profile that is central to systemic treatment selection.
pMMR/MSS tumours lack the deficient DNA mismatch-repair machinery associated with immune checkpoint inhibitor benefit. The concurrent presence of a RAS mutation (KRAS or NRAS) with BRAF wild-type further defines which systemic therapy combinations are appropriate for this population and which are not.
Systemic therapy for this molecular profile involves chemotherapy backbone regimens combined with selected targeted agents. The specific regimen chosen depends on prior treatment exposure. For patients with a KRAS G12C mutation, additional targeted options may apply. The complete regimen options, sequencing criteria, and selection algorithm are detailed in the full protocol.