title: KRAS mutations detected by the amplification refractory mutation system-Scorpion assays strongly correlate with therapeutic effect of cetuximab.
abstract: BACKGROUND
  We aimed to compare the sensitive and quality-controlled KRAS testing with direct sequencing and to assess the impact on decision making of treatment.
  
  
  METHODS
  We analysed genomic DNA isolated from macrodissected formalin-fixed paraffin-embedded specimens by direct sequencing and an amplification refractory mutation system-Scorpion assay (ARMS/S) method. Cetuximab was administered to patients identified as having wild-type (WT) KRAS using direct sequencing. Therapeutic effects were evaluated according to their KRAS status as determined by ARMS/S.
  
  
  RESULTS
  Among the 159 patients, the overall mutation rate was determined to be 37.0% by direct sequencing and 44.0% by ARMS/S. For the patients diagnosed as WT by direct sequencing and treated with cetuximab (n=47), a response rate of 16.0% was observed for 38 ARMS/S WT patients, whereas 9 ARMS/S mutant (MUT) patients failed to respond. The ARMS/S WT patients showed significant improvement in progression-free survival (PFS) and overall survival (OS) compared with ARMS/S MUT patients (PFS median 5.0 vs 1.7 months, hazards ratio (HR)=0.29, P=0.001; OS median 12.1 vs 3.8 months, HR=0.26, P=0.001).
  
  
  CONCLUSIONS
  Sensitive and quality-controlled KRAS testing may provide improved predictive power to determine the efficacy of anti-epidermal growth factor antibodies.
authors: Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba 277-8577, Japan.
authors: H
authors: H
authors: Bando
authors: T
authors: T
authors: Yoshino
authors: K
authors: K
authors: Tsuchihara
authors: N
authors: N
authors: Ogasawara
authors: N
authors: N
authors: Fuse
authors: T
authors: T
authors: Kojima
authors: M
authors: M
authors: Tahara
authors: M
authors: M
authors: Kojima
authors: K
authors: K
authors: Kaneko
authors: T
authors: T
authors: Doi
authors: A
authors: A
authors: Ochiai
authors: H
authors: H
authors: Esumi
authors: A
authors: A
authors: Ohtsu
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality; D004252:DNA Mutational Analysis / Q000379:methods*; D018572:Disease-Free Survival; D005260:Female; D011905:Genes, ras; D006801:Humans; D008297:Male; D009154:Mutation; D017422:Sequence Analysis, DNA / Q000379:methods
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068818:Cetuximab