title: pERK, pAKT and p53 as tissue biomarkers in erlotinib-treated patients with advanced pancreatic cancer: a translational subgroup analysis from AIO-PK0104.
abstract: BACKGROUND
  The role of pERK, pAKT and p53 as biomarkers in patients with advanced pancreatic cancer has not yet been defined.
  
  
  METHODS
  Within the phase III study AIO-PK0104 281 patients with advanced pancreatic cancer received an erlotinib-based 1st-line regimen. Archival tissue from 153 patients was available for central immunohistochemistry staining for pERK, pAKT and p53. Within a subgroup analysis, biomarker data were correlated with efficacy endpoints and skin rash using a Cox regression model.
  
  
  RESULTS
  Fifty-five out of 153 patients were classified as pERKlow and 98 patients as pERKhigh; median overall survival (OS) was 6.2 months and 5.7 months, respectively (HR 1.29, p = 0.16). When analysing pERK as continuous variable, the pERK score was significantly associated with OS (HR 1.06, 95% CI 1.0-1.12, p = 0.05). Twenty-one of 35 patients were pAKTlow and 14/35 pAKThigh with a corresponding median OS of 6.4 months and 6.8 months, respectively (HR 1.03, p = 0.93). Four out of 50 patients had a complete loss of p53 expression, 20 patients a regular expression and 26 patients had tumors with p53 overexpression. The p53 status had no impact on OS (p = 0.91); however, a significant improvement in progression-free survival (PFS) (6.0 vs 1.8 months, HR 0.24, p = 0.02) and a higher rate of skin rash (84% vs 25%, p = 0.02) was observed for patients with a regular p53 expression compared to patients with a complete loss of p53.
  
  
  CONCLUSIONS
  pERK expression may have an impact on OS in erlotinib-treated patients with advanced pancreatic cancer; p53 should be further investigated for its potential role as a predictive marker for PFS and skin rash.
  
  
  BACKGROUND
  NCT00440167 (registration date: February 22, 2007).
authors.forename: Steffen
authors.initials: S
authors.lastname: Ormanns
authors.forename: Jens T
authors.initials: JT
authors.lastname: Siveke
authors.forename: Volker
authors.initials: V
authors.lastname: Heinemann
authors.forename: Michael
authors.initials: M
authors.lastname: Haas
authors.forename: Bence
authors.initials: B
authors.lastname: Sipos
authors.forename: Anna Melissa
authors.initials: AM
authors.lastname: Schlitter
authors.forename: Irene
authors.initials: I
authors.lastname: Esposito
authors.forename: Andreas
authors.initials: A
authors.lastname: Jung
authors.forename: Rüdiger P
authors.initials: RP
authors.lastname: Laubender
authors.forename: Stephan
authors.initials: S
authors.lastname: Kruger
authors.forename: Ursula
authors.initials: U
authors.lastname: Vehling-Kaiser
authors.forename: Cornelia
authors.initials: C
authors.lastname: Winkelmann
authors.forename: Ludwig
authors.initials: L
authors.lastname: Fischer von Weikersthal
authors.forename: Michael R
authors.initials: MR
authors.lastname: Clemens
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Gauler
authors.forename: Angela
authors.initials: A
authors.lastname: Märten
authors.forename: Michael
authors.initials: M
authors.lastname: Geissler
authors.forename: Tim F
authors.initials: TF
authors.lastname: Greten
authors.forename: Thomas
authors.initials: T
authors.lastname: Kirchner
authors.affiliation: Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, München, Germany. stefan.boeck@med.uni-muenchen.de.
authors.forename: Stefan
authors.initials: S
authors.lastname: Boeck
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism*; D000069347:Erlotinib Hydrochloride; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult; D019892:eIF-2 Kinase / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D011799:Quinazolines; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D000069347:Erlotinib Hydrochloride; C460640:EIF2AK3 protein, human; D051057:Proto-Oncogene Proteins c-akt; D019892:eIF-2 Kinase; D048049:Extracellular Signal-Regulated MAP Kinases