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HER2+ IHC 3+

Prognosis
2.00% Prevalence Level 2 HER2 Pathway
Actionable Target
FDA-approved targeted therapies or strong clinical trial evidence available
Genes Involved
HER2
Treatment Implications

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 Treatments
Tucatinib + Trastuzumab (if RAS WT)
Trastuzumab Deruxtecan 5.4 mg/kg
Trastuzumab + Pertuzumab
Zanidatamab + chemotherapy
Treatments to Avoid

No specific contraindications noted

Study References

MOUNTAINEER, DESTINY-CRC02, MyPathway, HERACLES

Key Statistics
2.00%
Prevalence in CRC
Yes
Targetable
Clinical Notes
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).
Information

Category: HER2 Pathway

Evidence Level: Level 2

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.