Back to All Combinations

HER2 + KRAS Co-Mutation

Prognosis
0.50% Prevalence Level 2 HER2 Pathway
Actionable Target
FDA-approved targeted therapies or strong clinical trial evidence available
Genes Involved
HER2 KRAS
Treatment Implications

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 Treatments
Trastuzumab Deruxtecan (T-DXd) 5.4 mg/kg
Standard chemotherapy + Bevacizumab
Clinical trials
Treatments to Avoid

No specific contraindications noted

Study References

DESTINY-CRC02 (PMID: 39116902)

Key Statistics
0.50%
Prevalence in CRC
Yes
Targetable
Clinical Notes
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%).
Information

Category: HER2 Pathway

Evidence Level: Level 2

Last Updated: Dec 21, 2025

Related Combinations
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.