Abstract:

BACKGROUND: The KRAS mutation has been associated with resistance to cetuximab, an anti-epidermal growth factor receptor (EGFR) monoclonal antibody, in metastatic colorectal cancer (mCRC). However, the predictive biomarkers of cetuximab resistance in KRAS wild-type mCRC remain unknown except BRAF, NRAS, and PIK3CA exon 20. The objective of the study is to study the impact of EGFR L2 mutations on resistance to cetuximab in KRAS wild-type patients.
PATIENTS AND METHODS: A total of 247 mCRC patients were screened for KRAS status at the National Cancer Center Hospital between September 2008 and April 2010. We analyzed the EGFR L2 domain mutation status in KRAS wild type and in the patients treated with cetuximab-based therapy.
RESULTS: There were 136 patients with wild-type KRAS (55%). Sixty-five patients were analyzed for the L2 domain mutation status, and all patients received cetuximab-based therapy. One patient who had a mutation at exon 9 showed a partial response to cetuximab plus irinotecan.
CONCLUSION: Mutation of the EGFR L2 domain was analyzed in mCRC patients. Our findings do not provide sufficient evidence that EGFR L2 domain mutation is correlated with resistance to cetuximab.

日本語要旨:

大腸がんのEGFR細胞外ドメイン変異の頻度は少なく、cetuximabの効果との相関もなさそう。