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
MET Amplification + RAS WT
Intermediate
MET Amplification RAS Wild-type
2.00% prevalence Actionable

Recommended
MET inhibitors (clinical trials) Capmatinib Tepotinib
General
C
HER2+ IHC 3+
HER2
2.00% prevalence Actionable

Best outcomes with anti-HER2 therapy. Options: Tucatinib + Trastuzumab (if RAS WT), Trastuzumab Deruxtecan (regardless of RAS), Trastuzumab + Pertuzumab, Zanidatamab combinations. IHC 3+ patients have higher response rates across all anti-HER2 studies.

Recommended
Tucatinib + Trastuzumab (if RAS WT) Trastuzumab Deruxtecan 5.4 mg/kg Trastuzumab + Pertuzumab +1 more
HER2 Pathway
Level 2
POLE/POLD1 Ultramutated
Good
POLE POLD1
1.00% prevalence Actionable

Ultramutated (>100 mut/Mb). Exceptional immunotherapy responders.

Recommended
Pembrolizumab Nivolumab
Immunotherapy Biomarkers
Level 2B
HER2 + KRAS Co-Mutation
HER2 KRAS
0.50% prevalence Actionable

UPDATED 2024: Trastuzumab Deruxtecan (T-DXd) 5.4 mg/kg - DESTINY-CRC02 showed efficacy regardless of RAS status. ORR 37.8% in RAS mutant patients. NOTE: Tucatinib + Trastuzumab (MOUNTAINEER) requires RAS wild-type and is NOT appropriate for this combination.

Recommended
Trastuzumab Deruxtecan (T-DXd) 5.4 mg/kg Standard chemotherapy + Bevacizumab Clinical trials
HER2 Pathway
Level 2
NTRK Fusion
Good
NTRK1 NTRK2 NTRK3
0.50% prevalence Actionable

Rare but dramatic responses >75% ORR. Tumor-agnostic approval.

Recommended
Larotrectinib Entrectinib Repotrectinib
Rare Fusions
Level 1
FAP/AFAP
Intermediate
APC
0.50% prevalence Actionable

Hereditary polyposis. May need colectomy.

Recommended
Surgery Celecoxib Family screening
Special Populations
Level 1
KRAS G12C + STK11
Intermediate
KRAS G12C STK11
0.50% prevalence Actionable

Recommended
Sotorasib + Panitumumab Adagrasib + Cetuximab
Avoid
Immunotherapy alone
General
B
NTRK Fusion + Any
Intermediate
NTRK Fusion
0.50% prevalence Actionable

Recommended
Larotrectinib Entrectinib
General
A
NRG1 Fusion
Intermediate
NRG1 HER3
0.30% prevalence Actionable

Rare but targetable. Zenocutuzumab shows promise.

Recommended
Zenocutuzumab Clinical trials
HER2 Pathway
Level 2B
MUTYH Polyposis
Intermediate
MUTYH
0.30% prevalence Actionable

Autosomal recessive. Biallelic mutations needed.

Recommended
Surgery Surveillance Family testing
Special Populations
Level 2A
RET Fusion + Any
Intermediate
RET Fusion
0.30% prevalence Actionable

Recommended
Selpercatinib Pralsetinib
General
B
KRAS G13D + HER2+
KRAS HER2
0.30% prevalence Actionable

Trastuzumab Deruxtecan (T-DXd) 5.4 mg/kg - DESTINY-CRC02 demonstrated efficacy regardless of KRAS status. ORR ~38% in RAS mutant patients. NOTE: Tucatinib + Trastuzumab (MOUNTAINEER) requires RAS wild-type, NOT appropriate here.

Recommended
Trastuzumab Deruxtecan (T-DXd) 5.4 mg/kg Standard chemotherapy + Bevacizumab Clinical trials
Avoid
Tucatinib + Trastuzumab (requires RAS WT) Anti-EGFR therapy
HER2 Pathway
Level 2
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.