Prognostic Role of HER2 Amplification and Mutations in Metastatic Colorectal Cancer: Insights from Eight Randomized Trials

Highlight

1. HER2 amplification/overexpression occurs in approximately 5% of RAS/BRAF wild-type metastatic colorectal cancers (mCRCs) and is associated with worse progression-free and overall survival.
2. HER2 mutations, although less common (2% of HER2-negative tumors), similarly link to poorer overall survival.
3. Neither HER2 amplification nor mutation status predicts benefit from chemotherapy combined with bevacizumab or anti-EGFR monoclonal antibodies.
4. These findings support HER2 alteration status as a negative prognostic factor, not predictive of biologic agent efficacy, in proficient mismatch repair (pMMR)/microsatellite stable (MSS) RAS/BRAF wild-type mCRC.

Study Background and Disease Burden