pERK, pAKT and p53 as tissue biomarkers in erlotinib-treated patients with advanced pancreatic cancer: a translational subgroup analysis from AIO-PK0104
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
BMC Cancer 2014, 14:624 doi:10.1186/1471-2407-14-624Published: 28 August 2014
The role of pERK, pAKT and p53 as biomarkers in patients with advanced pancreatic cancer has not yet been defined.
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.
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.
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.
NCT00440167 (registration date: February 22, 2007).