title: Clinical benefit of high-sensitivity KRAS mutation testing in metastatic colorectal cancer treated with anti-EGFR antibody therapy.
abstract: OBJECTIVE
  We compared high-sensitivity KRAS mutation testing with direct sequencing for predicting the efficacy of antiepidermal growth factor receptor antibodies in patients with metastatic colorectal cancer (mCRC).
  
  
  METHODS
  We analyzed the KRAS status in 61 tumors from cetuximab-treated mCRC patients by both direct sequencing and a high-sensitivity method: 2-step PCR restriction fragmentation length polymorphism (RFLP). Therapeutic effects in each mutational status were evaluated.
  
  
  RESULTS
  The incidences of KRAS mutations determined by direct sequencing and 2-step PCR RFLP were 34.4 and 52.5%, respectively (p = 0.02). Patients were categorized into 3 groups [W/W, wild-type by both methods (n = 29); W/M, wild-type by direct sequencing, detected mutation by 2-step PCR RFLP (n = 11); M/M, mutant-type by both methods (n = 21)]. The response rate for cetuximab in the W/M group (0%) was the same as that in the M/M group, and was significantly lower than in the W/W group (41.4%) (p < 0.001). Progression-free survival in the W/M group (11.0 weeks) was similar to that in the M/M group (8.0 weeks), and was significantly shorter than in the W/W group (18.0 weeks) (p < 0.002).
  
  
  CONCLUSIONS
  High-sensitivity KRAS mutation testing is useful for selecting true responders to cetuximab.
authors.affiliation: Department of Gastroenterology and Oncology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Kimura
authors.forename: Koichi
authors.initials: K
authors.lastname: Okamoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Miyamoto
authors.forename: Masako
authors.initials: M
authors.lastname: Kimura
authors.forename: Shinji
authors.initials: S
authors.lastname: Kitamura
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Takenaka
authors.forename: Naoki
authors.initials: N
authors.lastname: Muguruma
authors.forename: Toshiya
authors.initials: T
authors.lastname: Okahisa
authors.forename: Eriko
authors.initials: E
authors.lastname: Aoyagi
authors.forename: Mayumi
authors.initials: M
authors.lastname: Kajimoto
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Tsuji
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kogawa
authors.forename: Akihito
authors.initials: A
authors.lastname: Tsuji
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Takayama
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000556:secondary; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D012189:Retrospective Studies; D018631:ras Proteins / Q000235:genetics*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000068818:Cetuximab