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

Ormanns, Steffen; Siveke, Jens T; Heinemann, Volker; Haas, Michael; Sipos, Bence; Schlitter, Anna Melissa; Esposito, Irene; Jung, Andreas; Laubender, Rüdiger P; Kruger, Stephan; Vehling-Kaiser, Ursula; Winkelmann, Cornelia; Fischer von Weikersthal, Ludwig; Clemens, Michael R; Gauler, Thomas C; Märten, Angela; Geissler, Michael; Greten, Tim F; Kirchner, Thomas; Boeck, Stefan

doi:10.1186/1471-2407-14-624

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Title:: pERK, pAKT and p53 as tissue biomarkers in erlotinib-treated patients with advanced pancreatic cancer: a translational subgroup analysis from AIO-PK0104.
Document type:: Journal Article; Research Support, Non-U.S. Gov't
Author(s):: Ormanns, Steffen; Siveke, Jens T; Heinemann, Volker; Haas, Michael; Sipos, Bence; Schlitter, Anna Melissa; Esposito, Irene; Jung, Andreas; Laubender, Rüdiger P; Kruger, Stephan; Vehling-Kaiser, Ursula; Winkelmann, Cornelia; Fischer von Weikersthal, Ludwig; Clemens, Michael R; Gauler, Thomas C; Märten, Angela; Geissler, Michael; Greten, Tim F; Kirchner, Thomas; Boeck, Stefan
Abstract:: 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). «
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... »
Journal title abbreviation:: BMC Cancer
Year:: 2014
Journal volume:: 14
Pages contribution:: 624
Language:: eng
Fulltext / DOI:: doi:10.1186/1471-2407-14-624
Pubmed ID:: http://view.ncbi.nlm.nih.gov/pubmed/25164437
TUM Institution:: II. Medizinische Klinik und Poliklinik (Gastroenterologie); Institut für Allgemeine Pathologie und Pathologische Anatomie
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