What your mutation combination means
Tumour alterations rarely come alone. Here you can see how prognosis and treatment change depending on how they combine.
47 combinations
BRAF V600E + MSI-H BRAF V600EMSI-H
MSI-H status confers better prognosis even with BRAF mutation. Immunotherapy highly effective.
Recommended treatments
PembrolizumabNivolumab + IpilimumabMET Amplification + RAS WT MET AmplificationRAS Wild-type
May emerge as resistance mechanism to anti-EGFR therapy. MET inhibitors in development.
Recommended treatments
MET inhibitors (clinical trials)CapmatinibTepotinibHER2+ IHC 3+ HER2 Best outcomes with anti-HER2 therapy. Options: Tucatinib + Trastuzumab (if RAS WT), Trastuzumab Deruxtecan (regardless of RAS), Trastuzumab + Pertuzumab, Zanidatamab combinations.…
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.
IHC 3+ represents ~2% of mCRC but has best responses to anti-HER2. DESTINY-CRC02 showed superior outcomes in IHC 3+ vs IHC 2+/FISH+. Test with validated HER2 IHC assay. Consider central confirmation for borderline cases. First-line data emerging (Zanidatamab 91% ORR).
Recommended treatments
Tucatinib + Trastuzumab (if RAS WT)Trastuzumab Deruxtecan 5.4 mg/kgTrastuzumab + PertuzumabZanidatamab + chemotherapyHER2 + KRAS Co-Mutation HER2KRAS 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 (M…
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.
CRITICAL UPDATE 2024: DESTINY-CRC02 demonstrated T-DXd activity in HER2+ CRC regardless of RAS mutation status. This changes the treatment paradigm. Best results in IHC 3+ patients. Monitor for ILD (~10%).
Recommended treatments
Trastuzumab Deruxtecan (T-DXd) 5.4 mg/kgStandard chemotherapy + BevacizumabClinical trialsFAP/AFAP APC Hereditary polyposis. May need colectomy.
Hereditary polyposis. May need colectomy.
Extracolonic manifestations (desmoids, thyroid).
Recommended treatments
SurgeryCelecoxibFamily screeningKRAS G12C + STK11 KRAS G12CSTK11
Very rare in CRC (<1%). STK11 co-mutation impact less studied in CRC than NSCLC. KRAS G12C inhibitors remain primary treatment.
Recommended treatments
Sotorasib + PanitumumabAdagrasib + CetuximabTreatments to avoid
Immunotherapy aloneNTRK Fusion + Any NTRK Fusion
Rare but highly actionable. TRK inhibitors are tumor-agnostic approved.
Recommended treatments
LarotrectinibEntrectinibNRG1 Fusion NRG1HER3 Rare but targetable. Zenocutuzumab shows promise.
Rare but targetable. Zenocutuzumab shows promise.
Requires RNA-based NGS detection.
Recommended treatments
ZenocutuzumabClinical trialsMUTYH Polyposis MUTYH Autosomal recessive. Biallelic mutations needed.
Autosomal recessive. Biallelic mutations needed.
Recessive inheritance pattern.
Recommended treatments
SurgerySurveillanceFamily testingRET Fusion + Any RET Fusion
Rare but actionable with selective RET inhibitors.
Recommended treatments
SelpercatinibPralsetinibKRAS G13D + HER2+ KRASHER2 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 (MOUNTAINE…
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.
Rare but actionable combination (<1% of mCRC). CRITICAL: Unlike other anti-HER2 approaches, T-DXd works in KRAS mutant tumors. DESTINY-CRC02 showed no difference in response between RAS WT and RAS mutant patients. Best results in IHC 3+. Monitor for ILD.
Recommended treatments
Trastuzumab Deruxtecan (T-DXd) 5.4 mg/kgStandard chemotherapy + BevacizumabClinical trialsTreatments to avoid
Tucatinib + Trastuzumab (requires RAS WT)Anti-EGFR therapyRET Fusion RET Very rare but highly actionable.
Very rare but highly actionable.
Identify through comprehensive NGS.
Recommended treatments
SelpercatinibPralsetinibALK Fusion ALK Extremely rare. Case reports of responses.
Extremely rare. Case reports of responses.
Identified incidentally on NGS.
Recommended treatments
AlectinibLorlatinibCrizotinibROS1 Fusion ROS1 Ultra-rare. ROS1 inhibitors may help.
Ultra-rare. ROS1 inhibitors may help.
Entrectinib covers ROS1 and NTRK.
Recommended treatments
EntrectinibCrizotinibKRAS + APC KRASAPC
Very common combination. APC loss is an early event in most CRCs.
Recommended treatments
Standard chemotherapyBevacizumab-basedTreatments to avoid
Anti-EGFR monotherapyHow 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.