1. pERK, pAKT and p53 as tissue biomarkers in erlotinib-treated patients with advanced pancreatic cancer: a translational subgroup analysis from AIO-PK0104
- Author
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Ormanns, Steffen, Siveke, Jens, Heinemann, Volker, Haas, Michael L., Sipos, Bence, Schlitter, Anna Melissa Elissa, Esposito, Iréne, Jung, Andreas, Laubender, Rüdiger Paul Aul, Kruger, Stephan, Vehling-Kaiser, Ursula, Winkelmann, Cornelia, Fischer von Weikersthal, Ludwig, Clemens, Michael Roland, Gauler, Thomas, Märten, Angela, Geissler, Michael, Greten, Tim F., Kirchner, Thomas, and Boeck, Stefan
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Adult ,Male ,Cancer Research ,EGFR ,Medizin ,Biomarker ,Pancreatic cancer ,Middle Aged ,Survival Analysis ,Pancreatic Neoplasms ,Erlotinib Hydrochloride ,Young Adult ,eIF-2 Kinase ,Erlotinib ,Oncology ,Biomarkers, Tumor ,Quinazolines ,Genetics ,Humans ,Female ,Phosphorylation ,Tumor Suppressor Protein p53 ,Extracellular Signal-Regulated MAP Kinases ,Proto-Oncogene Proteins c-akt ,Research Article - 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). Electronic supplementary material The online version of this article (doi:10.1186/1471-2407-14-624) contains supplementary material, which is available to authorized users.
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