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KRAS G13D + HER2+

Prognosis
0.30% Prevalence Level 2 HER2 Pathway
Actionable Target
FDA-approved targeted therapies or strong clinical trial evidence available
Genes Involved
KRAS HER2
Treatment Implications

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.

Recommended Treatments
Trastuzumab Deruxtecan (T-DXd) 5.4 mg/kg
Standard chemotherapy + Bevacizumab
Clinical trials
Treatments to Avoid
Tucatinib + Trastuzumab (requires RAS WT)
Anti-EGFR therapy
Study References

DESTINY-CRC02 (PMID: 39116902)

Key Statistics
0.30%
Prevalence in CRC
Yes
Targetable
Clinical Notes
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.
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.