The status of EGFR-associated genes could predict the outcome and tumor response of chemo-refractory metastatic colorectal patients using cetuximab and chemotherapy.

PURPOSE

This study was designed to analyze the impacts of status of EGFR-associated genes on the outcome of chemo-refractory mCRC patients using cetuximab.

MATERIALS AND METHODS

We collected samples from 42 metastatic CRC patients refractory to FOLFOX or FOLFIRI. Mutation profiles of KRAS, BRAF, PTEN, and PI3KCA and the copy numbers of EGFR and PTEN were analyzed. Overall survival and tumor response between various statuses of EGFR-associated genes were compared.

RESULTS

Eleven patients had a partial response to cetuximab with chemotherapy. Sixteen (38.1%) tumors had KRAS mutations. Three (7.1%) had BRAF mutations (V600E) and three (7.1%) had PTEN mutations. No PIK3CA mutation was found. Of 26 wild-KRAS tumors, nine (34.6%) had a partial response to cetuximab: this was higher than that of KRAS-mutated tumors (12.5%). Five patients with BRAF or PTEN mutations did not response to cetuximab. Response rate increased to 45% in patients with all wild-type KRAS, BRAF, and PTEN tumors. Of 16 tumors with high EGFR copy number, eight (50%) responded to cetuximab, a higher response rate than that of tumors with normal EGFR copy number (3/26, P = 0.011). Overall survival of patients was associated with high EGFR copy number and all wild-type tumors.

CONCLUSION

EFGR copy number and mutation in EGFR-associated genes could be selective markers in mCRC patients using cetuximab.