HER-2 gene alterations as biomarker in patients with metastatic colorectal cancer treated with FOLFIRI + cetuximab: findings from the CAPRI-2 GOIM study.

BACKGROUND

Human epidermal growth factor receptor 2 (HER-2) overexpression/amplification is a known prognostic and predictive biomarker in breast and gastric cancer. However, its role in metastatic colorectal cancer (mCRC) is still debated.

PATIENTS AND

METHODS

We conducted an exploratory analysis to investigate the role of HER-2 amplifications/mutations in patients with RAS/BRAF V600 wild type (WT), microsatellite stable (MSS) mCRC enrolled in the CAPRI-2 GOIM trial, who received FOLFIRI/cetuximab as first-line therapy. At baseline, plasma and tumor tissue samples were collected for comprehensive genomic profiling using the FoundationOne CDx assay. HER-2 positive tumors were defined in case of HER-2 mutations or gene amplification, defined by using a gene copy number cut-off of ≥4.

RESULTS

Patients with HER-2 negative tumors had numerically higher objective response rates [78% versus 60%; odd-ratio, 1.95, 95% confidence interval (CI): 0.47-8; P = 0.4] compared with HER-2 positive tumors. Patients with HER-2 positive mCRC had worse median progression-free survival (PFS) [(7.54 months; 95% CI:4.99-Not evaluable (NE) versus 13.47 months (95% CI: 11.76-16.3); hazard ratio (HR): 2.47; 95% CI: 1.27-4.65; P = 0.007] as well as worse median overall survival [16.4 months (95% CI:9.4-NE) versus 33.4 (30.36-NE); HR: 2.54; 95% CI: 1.09-5.93; P = 0.031] compared with patients with HER-2 negative tumors. Of note, 6/7 cases with HER-2 mutations exhibited limited benefit from treatment with FOLFIRI plus cetuximab with PFS inferior to 8 months.

CONCLUSION

Taken together, these results highlight the need to test HER-2 gene alterations for patients with RAS/BRAF V600 WT, MSS mCRC, who are candidates for anti-epidermal growth factor receptor therapies.