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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2014-12

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

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). More... »

PAGES

624

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/1471-2407-14-624

DOI

http://dx.doi.org/10.1186/1471-2407-14-624

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1020451601

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/25164437


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