title: KRAS mutation status is not predictive for objective response to anti-EGFR treatment with erlotinib in patients with advanced pancreatic cancer.
abstract: BACKGROUND
  It has not yet been defined if KRAS has a prognostic value or is a predictive biomarker for the efficacy of erlotinib in advanced pancreatic cancer (PC).
  
  
  METHODS
  AIO-PK0104 was a phase III trial comparing gemcitabine/erlotinib followed by capecitabine with capecitabine/erlotinib followed by gemcitabine in advanced PC. For this post hoc subgroup analysis, biomarker data on the KRAS exon 2 mutation status were correlated with objective response to 1st-line therapy and with overall survival after start of 2nd-line chemotherapy (OSc).
  
  
  RESULTS
  KRAS codon 12 was mutated in 121 of 173 (70 %) patients. The KRAS status showed no association with objective response (p = 0.40), but KRAS wildtype patients had an improved OS (HR 1.68, p = 0.005). A trend for a survival benefit was also observed during (non-erlotinib containing) 2nd-line chemotherapy, with a HR of 1.47 (p = 0.10) for the OSc.
  
  
  CONCLUSIONS
  This post hoc analysis of AIO-PK0104 supports the assumption that KRAS is rather a prognostic than a predictive biomarker in PC.
authors: Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Marchioninistr. 15, 81377, Munich, Germany. stefan.boeck@med.uni-muenchen.de
authors: Stefan
authors: S
authors: Boeck
authors: Andreas
authors: A
authors: Jung
authors: Rüdiger P
authors: RP
authors: Laubender
authors: Jens
authors: J
authors: Neumann
authors: Rosalind
authors: R
authors: Egg
authors: Clara
authors: C
authors: Goritschan
authors: Steffen
authors: S
authors: Ormanns
authors: Michael
authors: M
authors: Haas
authors: Dominik P
authors: DP
authors: Modest
authors: Thomas
authors: T
authors: Kirchner
authors: Volker
authors: V
authors: Heinemann
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics; D018592:Cross-Over Studies; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000069347:Erlotinib Hydrochloride; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D011799:Quinazolines / Q000008:administration & dosage*; D016896:Treatment Outcome; D018631:ras Proteins / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins