pERK, pAKT and p53 as tissue biomarkers in erlotinib-treated patients with advanced pancreatic cancer: a translational subgroup analysis from AIO-PK0104

BMC Cancer. 2014 Aug 28;14:624. doi: 10.1186/1471-2407-14-624.


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.

Conclusion: 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.

Trial registration: NCT00440167 (registration date: February 22, 2007).

Publication types

  • Clinical Trial, Phase III
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers, Tumor / metabolism*
  • Erlotinib Hydrochloride
  • Extracellular Signal-Regulated MAP Kinases / metabolism*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Quinazolines / adverse effects
  • Quinazolines / therapeutic use*
  • Survival Analysis
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*
  • Young Adult
  • eIF-2 Kinase / metabolism*


  • Biomarkers, Tumor
  • Quinazolines
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Erlotinib Hydrochloride
  • EIF2AK3 protein, human
  • Proto-Oncogene Proteins c-akt
  • eIF-2 Kinase
  • Extracellular Signal-Regulated MAP Kinases

Associated data