Open Access Research article

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

Steffen Ormanns1, Jens T Siveke2, Volker Heinemann345, Michael Haas3, Bence Sipos6, Anna Melissa Schlitter7, Irene Esposito7, Andreas Jung145, Rüdiger P Laubender458, Stephan Kruger3, Ursula Vehling-Kaiser9, Cornelia Winkelmann10, Ludwig Fischer von Weikersthal11, Michael R Clemens12, Thomas C Gauler13, Angela Märten14, Michael Geissler15, Tim F Greten16, Thomas Kirchner145 and Stefan Boeck3*

Author Affiliations

1 Institute of Pathology, Ludwig-Maximilians-University of Munich, München, Germany

2 Department of Internal Medicine II, Klinikum Rechts der Isar, Technische Universität München, München, Germany

3 Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, München, Germany

4 German Cancer Consortium (DKTK), Heidelberg, Germany

5 German Cancer Research Center (DKFZ), Heidelberg, Germany

6 Institute of Pathology, University of Tübingen, Tübingen, Germany

7 Institute of Pathology, Technische Universität München, München, Germany

8 Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-University of Munich, München, Germany

9 Practice for Medical Oncology, Landshut, Germany

10 Department of Internal Medicine, Krankenhaus Lutherstadt-Wittenberg, Lutherstadt-Wittenberg, Germany

11 Department of Oncology, Gesundheitszentrum St. Marien GmbH, Amberg, Germany

12 Department of Internal Medicine I, Klinikum Mutterhaus Trier, Trier, Germany

13 Department of Medicine (Cancer Research), West German Cancer Center, University of Duisburg-Essen, Essen, Germany

14 Department of Surgery, University of Heidelberg, Heidelberg, Germany

15 Department of Gastroenterology and Oncology, Klinikum Esslingen, Esslingen am Neckar, Germany

16 Department of Gastroenterology, Hepatology and Endocrinology, Medical School Hannover, Hannover, Germany

For all author emails, please log on.

BMC Cancer 2014, 14:624  doi:10.1186/1471-2407-14-624

Published: 28 August 2014

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).

Keywords:
Biomarker; EGFR; Erlotinib; Pancreatic cancer