title: Association of K-ras mutational status and clinical outcomes in patients with metastatic colorectal cancer receiving panitumumab alone.
abstract: BACKGROUND
  Identifying predictive biomarkers is important to optimally treat patients. This analysis evaluated the association of K-ras, BRAF, and PIK3CA gene mutations with tumor resistance to panitumumab alone.
  
  
  METHODS
  From 3 phase II panitumumab metastatic colorectal cancer (mCRC) studies, 62 of 533 patient samples were available. Mutations were identified from genomic DNA by sequencing.
  
  
  RESULTS
  Of the 62 samples, 24 (38.7%) harbored a K-ras mutation, and 38 (61.3%) were wild type. In the wild-type K-ras group, 11% of patients had a partial response (PR), 53% had stable disease (SD), and 37% had progressive disease (PD). In the mutant K-ras group, 21% of patients had SD, and 79% of patients had PD; there were no responses. The absence of a K-ras mutation was associated with response to panitumumab (PR vs. SD vs. PD; P = .0028). The hazard ratio for wild-type versus mutant K-ras was 0.4 (95% CI, 0.2-0.7) for progression-free survival and 0.5 (95% CI, 0.3-0.9) for overall survival. Four patients had a V600E BRAF mutation, and 2 patients had a PIK3CA mutation.
  
  
  CONCLUSIONS
  These data suggest that patients with mCRC with activating K-ras mutations are less likely to respond to panitumumab alone. The small sample size limits us from defining a predictive role of PIK3CA and BRAF mutations for panitumumab treatment.
authors.affiliation: Department of Oncology Research, Amgen Inc, Thousand Oaks, CA 91320, USA. dfreeman@amgen.com
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Freeman
authors.forename: Todd
authors.initials: T
authors.lastname: Juan
authors.forename: Maureen
authors.initials: M
authors.lastname: Reiner
authors.forename: J Randolph
authors.initials: JR
authors.lastname: Hecht
authors.forename: Neal J
authors.initials: NJ
authors.lastname: Meropol
authors.forename: Jordan
authors.initials: J
authors.lastname: Berlin
authors.forename: Edith
authors.initials: E
authors.lastname: Mitchell
authors.forename: Ildiko
authors.initials: I
authors.lastname: Sarosi
authors.forename: Robert
authors.initials: R
authors.lastname: Radinsky
authors.forename: Rafael G
authors.initials: RG
authors.lastname: Amado
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics; D017322:Clinical Trials, Phase II as Topic; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000556:secondary; D004279:DNA, Viral / Q000032:analysis; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D000077544:Panitumumab; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D015996:Survival Rate; D016896:Treatment Outcome; D018631:ras Proteins / Q000235:genetics*
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D004279:DNA, Viral; D011518:Proto-Oncogene Proteins; D000077544:Panitumumab; D018631:ras Proteins