Impact of Human Epidermal Growth Factor Receptor 2 in Patients With Metastatic Colorectal Cancer Treated With Chemotherapy Plus Bevacizumab or Anti-EGFRs: Exploratory Analysis of Eight Randomized Trials.

This large analysis of 1,604 patients with proficient mismatch repair/microsatellite stable wild-type metastatic colorectal cancer (mCRC) evaluated the prognostic and predictive roles of HER2 amplification/overexpression (HER2-positive in 5% of cases) and activating mutations.

Key findings include:

• HER2-positive status was associated with shorter progression-free survival (median 9.8 vs. 12.2 months) and overall survival (28.0 vs. 34.9 months) compared to HER2-negative cases, despite similar objective response rates.
• No significant interaction was found between HER2 status and the efficacy of anti-EGFR or bevacizumab-based therapies.
• Activating mutations (present in 2% of patients) correlated with poorer overall survival but did not predict differential benefit from these biologic treatments.

Overall, HER2 positivity and activating mutations are negative prognostic factors in this population but do not currently predict response to anti-EGFR or bevacizumab therapies.