Mutation Combinations Database

Comprehensive guide to genetic mutation combinations in colorectal cancer, their clinical implications, and treatment recommendations.

64
Total Combinations
39
Actionable Targets
14
Categories
Showing 64 combinations
Third-Line Refractory
Any
100.00% prevalence Actionable

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.

Recommended
TAS-102 + Bevacizumab Fruquintinib Regorafenib +1 more
Treatment Line
Level 1
MSS (Immunotherapy Emerging)
MMR proficient
85.00% prevalence Actionable

EMERGING: Botensilimab + Balstilimab showing breakthrough activity (ORR 24%, DCR 73% in refractory MSS mCRC). FDA breakthrough therapy designation. Phase 3 trials ongoing. Standard options: Chemotherapy, TAS-102 + Bevacizumab (SUNLIGHT), Fruquintinib (FRESCO-2).

Recommended
Botensilimab + Balstilimab (clinical trials) TAS-102 + Bevacizumab Fruquintinib +2 more
Immunotherapy
Level 3
Left-Sided Primary
Good
Location
60.00% prevalence Actionable

Better prognosis. If RAS WT, strongly prefer anti-EGFR.

Recommended
If RAS WT: Anti-EGFR If RAS MT: Bevacizumab
Tumor Location
Level 1
Right-Sided Primary
Poor
Location
40.00% prevalence Actionable

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

Recommended
Intensive chemotherapy Bevacizumab-based
Tumor Location
Level 1
Acquired RAS (Post-Anti-EGFR)
Intermediate
KRAS NRAS
30.00% prevalence Actionable

RAS clones may decline after withdrawal. Rechallenge possible.

Recommended
Chemo holiday from anti-EGFR Liquid biopsy monitoring Anti-EGFR rechallenge
Avoid
Continuing anti-EGFR
Resistance Mechanisms
Level 2A
RAS/BRAF Wild-Type (Left)
Good
KRAS NRAS BRAF
25.00% prevalence Actionable

Best anti-EGFR candidates. PARADIGM showed superiority vs bevacizumab.

Recommended
FOLFOX + Panitumumab FOLFIRI + Cetuximab
RAS Pathway
Level 1
RAS WT + BRAF WT + Left-sided
Intermediate
RAS Wild-type BRAF Wild-type Left-sided
25.00% prevalence Actionable

Recommended
FOLFOX/FOLFIRI + Cetuximab FOLFOX/FOLFIRI + Panitumumab
General
A
ctDNA MRD Positive
Poor
ctDNA
20.00% prevalence Actionable

ctDNA MRD identifies high recurrence risk. DYNAMIC trial validated.

Recommended
Adjuvant chemotherapy Intensive surveillance
Emerging Targets
Level 2A
MSI-H / dMMR
Good
MLH1 MSH2 MSH6 PMS2
15.00% prevalence Actionable

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.

Recommended
Nivolumab + Ipilimumab (first-line) Pembrolizumab (first-line) Dostarlimab
Avoid
5-FU monotherapy
Immunotherapy Biomarkers
Level 1
Young-Onset CRC (<50)
Intermediate
Multiple
15.00% prevalence Actionable

Higher hereditary rate. Screen all for Lynch.

Recommended
MSI/MMR testing Germline testing Standard treatment
Special Populations
Level 2A
RAS/BRAF Wild-Type (Right)
Intermediate
KRAS NRAS BRAF
10.00% prevalence Actionable

Despite RAS WT, right-sided benefit less from anti-EGFR.

Recommended
FOLFOX + Bevacizumab FOLFOXIRI + Bevacizumab
RAS Pathway
Level 2A
BRAF V600E (MSS)
Poor
BRAF
8.00% prevalence Actionable

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).

Recommended
Encorafenib + Cetuximab + mFOLFOX6 (first-line) Encorafenib + Cetuximab (second-line) FOLFOXIRI + Bevacizumab
Avoid
Anti-EGFR monotherapy
BRAF Pathway
Level 1
About This Database

This database contains clinically relevant mutation combinations in colorectal cancer. Each combination includes:

  • Genes involved - The genetic alterations present
  • Prognosis - Expected outcome classification
  • Prevalence - How common in CRC patients
  • Recommended treatments - Evidence-based options
  • Treatments to avoid - Known ineffective therapies
  • Evidence level - Strength of supporting data

Actionable combinations have FDA-approved targeted therapies or strong clinical trial evidence. Always consult with your oncologist for personalized treatment decisions.