• Oncology · Jan 2009

    The role of KRAS mutations in predicting the efficacy of cetuximab-plus-irinotecan therapy in irinotecan-refractory Korean metastatic colorectal cancer patients.

    • Byeong Seok Sohn, Tae Won Kim, Jae-Lyun Lee, Min-Hee Ryu, Heung Moon Chang, Yoon-Koo Kang, Hyo Suk Park, Young-Soon Na, Se Jin Jang, Jin Cheon Kim, and Jung Shin Lee.
    • Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
    • Oncology. 2009 Jan 1; 77 (3-4): 224-30.

    ObjectiveThis study evaluated the clinical relevance of KRAS and BRAF mutational status in 66 irinotecan-refrac- tory Korean metastatic colorectal cancer (mCRC) patients treated with cetuximab-plus-irinotecan-based chemotherapy.MethodsA total of 66 irinotecan-refractory mCRC patients treated with cetuximab-plus-irinotecan-based chemotherapy were included. Tumors were screened for KRAS mutations (codons 12 and 13) and a BRAF mutation (V600E) using direct sequencing and the Snapshot assay.ResultsThe objective response rate (RR) for treatment was 21.2% (14/66) and skin rashes were observed in 43 (65.2%) of the 66 patients. A KRAS mutation was detected in 27 (40.9%) tumors, and was associated with lower RR (wild-type vs. mutated KRAS: 33.3 vs. 3.7%, p = 0.005) and shorter progression-free survival (PFS) and overall survival (OS; PFS: 6.4 vs. 2.0 months, p = 0.005; OS: 17.8 vs. 7.1 months, p = 0.001). Severe skin toxicity was associated with better RR and longer PFS and OS. BRAF mutations were not detected. Multivariate analysis revealed that KRAS status and skin toxicity were independent predictive factors of PFS and OS.ConclusionsThis study indicates the clinical relevance of KRAS mutations in predicting the efficacy of cetuximab-plus-irinotecan-based chemotherapy in irinotecan-refractory Korean mCRC patients.Copyright 2009 S. Karger AG, Basel.

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