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 und Boeck, Stefan (2014): pERK, pAKT and p53 as tissue biomarkers in erlotinib-treated patients with advanced pancreatic cancer: a translational subgroup analysis from AIO-PK0104. In: BMC Cancer 14:624

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 pERK(low) and 98 patients as pERK(high); 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 pAKT(low) and 14/35 pAKT(high) 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.

• Dokumententyp: Zeitschriftenartikel
• Publikationsform: Publisher's Version
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1471-2407
• Sprache: Englisch