title: Left-sided primary tumors are associated with favorable prognosis in patients with KRAS codon 12/13 wild-type metastatic colorectal cancer treated with cetuximab plus chemotherapy: an analysis of the AIO KRK-0104 trial.
abstract: OBJECTIVE
  AIO KRK-0104 investigated first-line therapy of metastatic colorectal cancer (mCRC) with cetuximab, capecitabine and irinotecan versus cetuximab, capecitabine and oxaliplatin. This analysis investigated the impact of primary tumor location on outcome of patients.
  
  
  METHODS
  Left-sided primary tumors were defined as tumors from rectum to left flexure, while tumors in the remaining colon were regarded right sided. Overall survival (OS), progression-free survival (PFS) and response rate were correlated with primary tumor location. A Cox regression model was used to evaluate interaction between primary tumor location and KRAS mutation.
  
  
  RESULTS
  Of 146 patients of the AIO KRK-0104 trial, 100 patients presented left-sided (of those 68 KRAS codon 12/13 wild-type) and 46 patients right-sided primary tumors (of those 27 KRAS codon 12/13 wild-type). Left-sided tumors were associated with significantly longer OS (p = 0.016, HR = 0.63) and PFS (p = 0.02, HR = 0.67) as compared to right-sided tumors. These effects were present in the KRAS codon 12/13 wild-type population (HR OS: 0.42; HR PFS: 0.54), while no impact of primary tumor location was evident in patients with KRAS codon 12/13 mutant tumors (HR OS: 1.3; HR PFS: 1.01). A significant interaction of KRAS status and primary tumor location concerning OS and PFS was observed.
  
  
  CONCLUSIONS
  Our findings suggest that primary tumor location and KRAS codon 12/13 mutational status interact on the outcome of patients with mCRC receiving cetuximab-based first-line therapy. Left-sided primary tumor location might be a predictor of cetuximab efficacy.
authors.affiliation: Department of Medicine III, University Hospital Grosshadern, University of Munich, Munich, Germany, jobst.von-einem@med.uni-muenchen.de.
authors.forename: J C
authors.initials: JC
authors.lastname: von Einem
authors.forename: V
authors.initials: V
authors.lastname: Heinemann
authors.forename: L Fischer
authors.initials: LF
authors.lastname: von Weikersthal
authors.forename: U
authors.initials: U
authors.lastname: Vehling-Kaiser
authors.forename: M
authors.initials: M
authors.lastname: Stauch
authors.forename: H G
authors.initials: HG
authors.lastname: Hass
authors.forename: T
authors.initials: T
authors.lastname: Decker
authors.forename: S
authors.initials: S
authors.lastname: Klein
authors.forename: S
authors.initials: S
authors.lastname: Held
authors.forename: A
authors.initials: A
authors.lastname: Jung
authors.forename: T
authors.initials: T
authors.lastname: Kirchner
authors.forename: M
authors.initials: M
authors.lastname: Haas
authors.forename: J
authors.initials: J
authors.lastname: Holch
authors.forename: M
authors.initials: M
authors.lastname: Michl
authors.forename: P
authors.initials: P
authors.lastname: Aubele
authors.forename: S
authors.initials: S
authors.lastname: Boeck
authors.forename: C
authors.initials: C
authors.lastname: Schulz
authors.forename: C
authors.initials: C
authors.lastname: Giessen
authors.forename: S
authors.initials: S
authors.lastname: Stintzing
authors.forename: D P
authors.initials: DP
authors.lastname: Modest
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068818:Cetuximab; D003062:Codon / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D018631:ras Proteins / Q000235:genetics*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D003062:Codon; D018631:ras Proteins; D000068818:Cetuximab