Mutation combinations

What your mutation combination means

Tumour alterations rarely come alone. Here you can see how prognosis and treatment change depending on how they combine.

64 combinations 39 with targeted treatment 14 categories
All Prognosis favourable Prognosis intermediate Prognosis unfavourable With targeted treatment
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4 combinations

Third-Line Refractory Prognosis unfavourable Targeted treatment 100% of cases Any STANDARD (SUNLIGHT): TAS-102 + Bevacizumab (OS 10.8mo vs 7.5mo, new standard 2023). ALTERNATIVE: Fruquintinib (FRESCO-2, OS 7.4mo). Regorafenib (CORRECT, OS 6.4mo). Consider clini…

STANDARD (SUNLIGHT): TAS-102 + Bevacizumab (OS 10.8mo vs 7.5mo, new standard 2023). ALTERNATIVE: Fruquintinib (FRESCO-2, OS 7.4mo). Regorafenib (CORRECT, OS 6.4mo). Consider clinical trials. Re-test for actionable mutations.

Updated 2023: SUNLIGHT trial established TAS-102 + Bevacizumab as preferred third-line option. Superior to TAS-102 monotherapy (HR 0.61). Fruquintinib approved as additional option (FRESCO-2). Always check for targetable alterations before palliative therapy.

Recommended treatments

TAS-102 + BevacizumabFruquintinibRegorafenibClinical trials
Treatment line · Evidence: level 1 SUNLIGHTFRESCO-2CORRECT See full page
Right-Sided Primary Prognosis unfavourable Targeted treatment 40% of cases Location Higher BRAF, MSI-H. Worse prognosis. Check MSI always.

Higher BRAF, MSI-H. Worse prognosis. Check MSI always.

Different biology regardless of RAS status.

Recommended treatments

Intensive chemotherapyBevacizumab-based
Tumour location · Evidence: level 1 CALGB 80405 See full page
ctDNA MRD Positive Prognosis unfavourable Targeted treatment 20% of cases ctDNA ctDNA MRD identifies high recurrence risk. DYNAMIC trial validated.

ctDNA MRD identifies high recurrence risk. DYNAMIC trial validated.

Transforming adjuvant decisions.

Recommended treatments

Adjuvant chemotherapyIntensive surveillance
Emerging targets · Evidence: level 2A DYNAMIC trial See full page
BRAF V600E (MSS) Prognosis unfavourable Targeted treatment 8% of cases BRAF FIRST-LINE (NEW 2025): Encorafenib + Cetuximab + mFOLFOX6 (BREAKWATER, OS 30.3 mo vs 15.1 mo - DOUBLES SURVIVAL). SECOND-LINE+: Encorafenib + Cetuximab doublet (BEACON, OS 9.3 mo).

FIRST-LINE (NEW 2025): Encorafenib + Cetuximab + mFOLFOX6 (BREAKWATER, OS 30.3 mo vs 15.1 mo - DOUBLES SURVIVAL). SECOND-LINE+: Encorafenib + Cetuximab doublet (BEACON, OS 9.3 mo).

BREAKWATER 2025: Practice-changing for first-line BRAF V600E mCRC. PFS 12.8 vs 7.1 mo, OS 30.3 vs 15.1 mo. FDA accelerated approval. Always test for MSI-H as BRAF V600E + MSI-H has better prognosis.

Recommended treatments

Encorafenib + Cetuximab + mFOLFOX6 (first-line)Encorafenib + Cetuximab (second-line)FOLFOXIRI + Bevacizumab

Treatments to avoid

Anti-EGFR monotherapy
BRAF pathway · Evidence: level 1 BREAKWATER (NEJM 2025)BEACON See full page

How 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.