• Hiroshi Soeda, Hideki Shimodaira, Makio Gamoh, Hideaki Ando, Hideki Isobe, Takeshi Suto, Shin Takahashi, Yuichi Kakudo, Kenji Amagai, Takahiro Mori, Mika Watanabe, Takuhiro Yamaguchi, Shunsuke Kato, and Chikashi Ishioka.
• Department of Clinical Oncology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
• Oncology. 2014 Jan 1; 87 (1): 7-20.

BackgroundMutations in the KRAS gene have been identified as negative predictors of response to anti-epidermal growth factor receptor (EGFR) monoclonal antibody therapy by patients with metastatic colorectal cancer (mCRC). However, it has been based on the study of mainly Caucasian mCRC patients. This prospective study investigated the relationship between the mutation status of EGFR-related genes including KRAS and the response rate (RR) to cetuximab plus irinotecan therapy in Japanese mCRC patients.MethodsSamples taken from 43 chemotherapy-refractory mCRC patients who had undergone cetuximab plus irinotecan therapy at 11 medical centers in Japan were subjected to direct DNA sequencing to determine the KRAS, BRAF, PIK3CA, NRAS, and AKT1 mutation status. The clinical outcome after the treatment was evaluated for each mutation status.ResultsKRAS mutations were detected in 31.7% of 41 eligible patients. The RR to cetuximab plus irinotecan therapy was found to be 17.9 and 0% in the KRAS wild-type and mutant subgroups, respectively.ConclusionDespite the identification of a lower-than-expected RR to treatment by the KRAS wild-type subgroup, KRAS mutation status appears to be a useful predictive marker of response to cetuximab plus irinotecan therapy in Japanese mCRC patients.© 2014 S. Karger AG, Basel.

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