Mutation Combinations Database
Comprehensive guide to genetic mutation combinations in colorectal cancer, their clinical implications, and treatment recommendations.
BRAF V600E + MSS
IntermediateFIRST-LINE: Encorafenib + Cetuximab + mFOLFOX6 (BREAKWATER, OS 30.3mo). SECOND-LINE+: Encorafenib + Cetuximab (BEACON). Note: MSS BRAF V600E has very poor prognosis without targeted therapy.
Recommended
Encorafenib + Cetuximab + mFOLFOX6 (first-line) Encorafenib + Cetuximab (second-line)Avoid
Standard doublet chemotherapy alone Anti-EGFR monotherapyPIK3CA Exon 20
IntermediateStrong aspirin benefit data. Regular aspirin improves survival.
Recommended
Standard chemotherapy Aspirin PI3K inhibitor trialsTMB-High (≥10 mut/Mb)
IntermediateFDA-approved tumor-agnostic biomarker for pembrolizumab.
Recommended
PembrolizumabMSI-H + BRAF WT
IntermediateRecommended
Pembrolizumab first-line Nivolumab + IpilimumabKRAS G12C
IntermediateFirst targetable KRAS! Sotorasib/adagrasib + anti-EGFR show ~30% ORR.
Recommended
Sotorasib + Panitumumab Adagrasib + Cetuximab Sotorasib +1 moreAvoid
Anti-EGFR monotherapyHER2 Amplified (RAS WT)
IntermediateFDA APPROVED: Tucatinib + Trastuzumab (MOUNTAINEER, ORR 38%, OS 24.1mo, approved Jan 2023). Also: T-DXd 5.4mg/kg (DESTINY-CRC02), Trastuzumab + Pertuzumab (MyPathway). First-line: Zanidatamab + chemo showing 91% ORR in early data.
Recommended
Tucatinib + Trastuzumab Trastuzumab Deruxtecan 5.4 mg/kg Trastuzumab + Pertuzumab +1 moreAvoid
Anti-EGFR monotherapyLynch Syndrome
GoodHereditary. MSI-H tumors respond to immunotherapy. Family screening essential.
Recommended
Immunotherapy Surveillance Family counselingHER2+ + RAS WT
IntermediateTucatinib + Trastuzumab (MOUNTAINEER, ORR 38%, OS 24.1mo, FDA approved Jan 2023). Trastuzumab Deruxtecan 5.4mg/kg (DESTINY-CRC02). Trastuzumab + Pertuzumab. Consider Zanidatamab combinations in trials.
Recommended
Tucatinib + Trastuzumab Trastuzumab Deruxtecan 5.4 mg/kg Trastuzumab + PertuzumabTMB-High + MSS
IntermediateRecommended
Pembrolizumab (FDA approved for TMB-H) Consider combination immunotherapyMSI-H + BRAF V600E (Sporadic)
IntermediateBetter than BRAF V600E/MSS. Usually sporadic with MLH1 methylation.
Recommended
Pembrolizumab Nivolumab + Ipilimumab Encorafenib + CetuximabAvoid
Anti-EGFR monotherapyEGFR S492R
IntermediateBlocks cetuximab but panitumumab still binds.
Recommended
Switch to PanitumumabAvoid
Continue CetuximabBRAF V600E + MSI-H
IntermediateRecommended
Pembrolizumab Nivolumab + IpilimumabAbout 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.