Biomarkers in tissue from patients with upper gastrointestinal cancers treated with erlotinib and bevacizumab

• Published in: Cancer biology & therapy Vol. 11; no. 8; pp. 732 - 739
• Main Authors: Rohrberg, Kristoffer Staal, Pappot, Helle, Lassen, Ulrik, Westman, Maj, Olesen, René K., Pfeiffer, Per, Ladekarl, Morten, Sørensen, Morten, Christensen, Ib J., Skov, Birgit G.
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 15-04-2011
• Subjects: Adult; Aged; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Humanized; Antineoplastic Agents - therapeutic use; Bevacizumab; Binding; Biology; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Bioscience; Calcium; Cancer; Cell; Cycle; ErbB Receptors - metabolism; Erlotinib Hydrochloride; Female; Gastrointestinal Neoplasms - drug therapy; Gastrointestinal Neoplasms - genetics; Gastrointestinal Neoplasms - metabolism; Gastrointestinal Neoplasms - pathology; Humans; Landes; Male; Middle Aged; Mutation - genetics; Organogenesis; Proteins; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins p21(ras); Quinazolines - therapeutic use; ras Proteins - genetics; Survival Analysis; Treatment Outcome; Vascular Endothelial Growth Factor A - metabolism; Vascular Endothelial Growth Factor Receptor-2 - metabolism
• ISSN: 1538-4047; 1555-8576
• DOI: 10.4161/cbt.11.8.14889

Malignancies in the upper gastrointestinal (UGI) tract are amongst the most aggressive cancers and only few treatment options exist. We have recently analysed data from a phase II trial where patients with UGI cancers were treated with erlotinib and bevacizumab. The combination therapy could not be recommended in an unselected population of patients with chemo-refractory UGI cancer. However, a subpopulation of patients did benefit from the therapy. In this prospectively planned biomarker study we investigated vascular endothelial growth factor A (VEGF-A), VEGF receptor 2 (VEGFR-2) and epidermal growth factor receptor (EGFR) by immunohistochemistry and KRAS mutation status detected by PCR as potential predictors of effect of therapy. High VEGF-A expression was correlated to longer overall survival (HR: 0.8, 95%CI: 0.7-0.9) and high VEGFR-2 expression to shorter progression free survival (HR: 1.4, 95%CI: 1.0-1.9). EGFR expression and KRAS mutation status were not correlated to response or survival. We conclude that VEGF-A and VEGFR-2 could potentially be predictive markers in patients with UGI cancers treated with erlotinib and bevacizumab.