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HER2 Amplified (RAS WT)

Intermediate Prognosis
3.00% Prevalence Level 1 HER2 Pathway
Actionable Target
FDA-approved targeted therapies or strong clinical trial evidence available
Genes Involved
HER2 ERBB2
Treatment Implications

FDA 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 Treatments
Tucatinib + Trastuzumab
Trastuzumab Deruxtecan 5.4 mg/kg
Trastuzumab + Pertuzumab
Zanidatamab + chemotherapy
Treatments to Avoid
Anti-EGFR monotherapy
Study References

MOUNTAINEER (PMID: 37142372), DESTINY-CRC02 (PMID: 39116902)

Key Statistics
3.00%
Prevalence in CRC
Yes
Targetable
Clinical Notes
HER2+ RAS WT has multiple FDA-approved options. MOUNTAINEER: Tucatinib + Trastuzumab approved Jan 2023. Test all mCRC for HER2 (IHC, FISH if 2+). Best outcomes in IHC 3+. MOUNTAINEER-03 testing first-line combination.
Information

Category: HER2 Pathway

Evidence Level: Level 1

Last Updated: Dec 21, 2025

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Medical Disclaimer: This information is for educational purposes only and should not replace professional medical advice. Always consult with your oncologist for personalized treatment decisions based on your specific situation.