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.

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).

• Authors: Steffen Ormanns, Jens T Siveke, Volker Heinemann, Michael Haas, Bence Sipos, Anna Melissa Schlitter, Irene Esposito, Andreas Jung, Rüdiger P Laubender, Stephan Kruger, Ursula Vehling-Kaiser, Cornelia Winkelmann, Ludwig Fischer von Weikersthal, Michael R Clemens, Thomas C Gauler, Angela Märten, Michael Geissler, Tim F Greten, Thomas Kirchner, Stefan Boeck
• Journal: BMC cancer (BMC Cancer) Vol. 14 Pg. 624 (Aug 28 2014) ISSN: 1471-2407 [Electronic] England
• PMID: 25164437 (Publication Type: Clinical Trial, Phase III, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 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

Topics

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