What your mutation combination means
Tumour alterations rarely come alone. Here you can see how prognosis and treatment change depending on how they combine.
7 combinations
Left-Sided Primary Location Better prognosis. If RAS WT, strongly prefer anti-EGFR.
Better prognosis. If RAS WT, strongly prefer anti-EGFR.
Sidedness is independent prognostic factor.
Recommended treatments
If RAS WT: Anti-EGFRIf RAS MT: BevacizumabRAS/BRAF Wild-Type (Left) KRASNRASBRAF Best anti-EGFR candidates. PARADIGM showed superiority vs bevacizumab.
Best anti-EGFR candidates. PARADIGM showed superiority vs bevacizumab.
Left-sided + RAS WT = anti-EGFR preferred.
Recommended treatments
FOLFOX + PanitumumabFOLFIRI + CetuximabMSI-H / dMMR MLH1MSH2MSH6PMS2 FIRST-LINE: Nivolumab + Ipilimumab (CheckMate-8HW, ORR 71%, 24mo PFS 72%) OR Pembrolizumab (KEYNOTE-177). CheckMate-8HW showed superiority over chemotherapy. Later lines: Nivoluma…
FIRST-LINE: Nivolumab + Ipilimumab (CheckMate-8HW, ORR 71%, 24mo PFS 72%) OR Pembrolizumab (KEYNOTE-177). CheckMate-8HW showed superiority over chemotherapy. Later lines: Nivolumab, Pembrolizumab, Dostarlimab.
Updated 2024: CheckMate-8HW established Nivo+Ipi as preferred first-line for MSI-H mCRC. ORR 71% vs 14% chemo, 24mo PFS 72% vs 14%. Prevalence: ~15% all stages, ~4-5% metastatic. Test all mCRC at diagnosis.
Recommended treatments
Nivolumab + Ipilimumab (first-line)Pembrolizumab (first-line)DostarlimabTreatments to avoid
5-FU monotherapyLynch Syndrome MLH1MSH2MSH6PMS2EPCAM Hereditary. MSI-H tumors respond to immunotherapy. Family screening essential.
Hereditary. MSI-H tumors respond to immunotherapy. Family screening essential.
Screen all CRC <50 and all MSI-H.
Recommended treatments
ImmunotherapySurveillanceFamily counselingPOLE/POLD1 Ultramutated POLEPOLD1 Ultramutated (>100 mut/Mb). Exceptional immunotherapy responders.
Ultramutated (>100 mut/Mb). Exceptional immunotherapy responders.
Screen for germline POLE/POLD1 (PPAP syndrome).
Recommended treatments
PembrolizumabNivolumabNTRK Fusion NTRK1NTRK2NTRK3 Rare but dramatic responses >75% ORR. Tumor-agnostic approval.
Rare but dramatic responses >75% ORR. Tumor-agnostic approval.
More common in MSI-H tumors.
Recommended treatments
LarotrectinibEntrectinibRepotrectinibWRN Deficient (MSI-H) WRN WRN helicase essential in MSI-H. Synthetic lethal approach.
WRN helicase essential in MSI-H. Synthetic lethal approach.
Multiple WRN inhibitors in early trials.
Recommended treatments
ImmunotherapyWRN inhibitor trialsHow to read this page
- Prognosis
- How the disease usually progresses with that combination compared with the average. It is a group trend, not a prediction for you.
- With targeted treatment
- There are approved or trial drugs that attack that specific alteration.
- Share of cases
- Roughly how many patients with metastatic colorectal cancer have that combination.
- Evidence
- How solid the data are: level 1 or grade A come from large trials; higher levels come from small or preliminary studies.
Educational information based on published studies. Your treatment is decided by your care team with all your data.