HER2 Alterations Predict Inferior Survival With Anti-EGFR Therapy in RAS/BRAF Wild-Type Metastatic Colorectal Cancer
Key Clinical Summary:
- Design/Population: Exploratory biomarker analysis of patients with RAS/BRAFV600 wild-type, microsatellite-stable metastatic colorectal cancer enrolled in the CAPRI-2 GOIM trial and treated with first-line FOLFIRI plus cetuximab. HER2 alterations were identified using comprehensive genomic profiling of plasma and tumor tissue.
- Key Outcomes: HER2-positive tumors were associated with significantly worse progression-free and overall survival compared with HER2-negative tumors. Patients with HER2 mutations in particular demonstrated limited benefit from anti-EGFR therapy.
- Clinical Relevance: These data support routine assessment of HER2 alterations in RAS/BRAFV600 wild-type, MSS metastatic colorectal cancer to refine patient selection for anti-EGFR therapies and avoid potentially ineffective treatment.
Davide Ciardiello, MD, European Institute of Oncology, Milan, Italy, discusses exploratory results from the CAPRI-2 GOIM trial evaluating the impact of HER2 alterations in patients with RAS/BRAFV600 wild-type, microsatellite-stable metastatic colorectal cancer treated with first-line FOLFIRI plus cetuximab.
Results demonstrated that HER2-positive tumors were associated with significantly shorter progression-free and overall survival compared with HER2-negative tumors. These findings suggest HER2 gene alterations may identify patients less likely to benefit from anti-EGFR therapy.
Source:
Ciardiello D, Bielo LB, Napolitano S, et al. HER-2 gene alterations as biomarker in patients with metastatic colorectal cancer treated with FOLFIRI + cetuximab: Findings from the CAPRI-2 GOIM study. ESMO Gastrointest Oncol. Published online: January 19, 2026. doi:10.1016/j.esmogo.2025.100295
