title: The role of KRAS mutations in predicting the efficacy of cetuximab-plus-irinotecan therapy in irinotecan-refractory Korean metastatic colorectal cancer patients.
abstract: OBJECTIVE
  This 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.
  
  
  METHODS
  A 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.
  
  
  RESULTS
  The 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.
  
  
  CONCLUSIONS
  This study indicates the clinical relevance of KRAS mutations in predicting the efficacy of cetuximab-plus-irinotecan-based chemotherapy in irinotecan-refractory Korean mCRC patients.
authors.affiliation: Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Byeong Seok
authors.initials: BS
authors.lastname: Sohn
authors.forename: Tae Won
authors.initials: TW
authors.lastname: Kim
authors.forename: Jae-Lyun
authors.initials: JL
authors.lastname: Lee
authors.forename: Min-Hee
authors.initials: MH
authors.lastname: Ryu
authors.forename: Heung Moon
authors.initials: HM
authors.lastname: Chang
authors.forename: Yoon-Koo
authors.initials: YK
authors.lastname: Kang
authors.forename: Hyo Suk
authors.initials: HS
authors.lastname: Park
authors.forename: Young-Soon
authors.initials: YS
authors.lastname: Na
authors.forename: Se Jin
authors.initials: SJ
authors.lastname: Jang
authors.forename: Jin Cheon
authors.initials: JC
authors.lastname: Kim
authors.forename: Jung Shin
authors.initials: JS
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D066246:ErbB Receptors / Q000235:genetics / Q000502:physiology; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D012867:Skin / Q000187:drug effects; D018631:ras Proteins / Q000235:genetics*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D000077146:Irinotecan; D066246:ErbB Receptors; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000068818:Cetuximab; D002166:Camptothecin