title: Biomarkers in tissue from patients with upper gastrointestinal cancers treated with erlotinib and bevacizumab.
abstract: 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.
authors.affiliation: Department of Oncology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark. kristoffer@onkolog.dk
authors.forename: Kristoffer Staal
authors.initials: KS
authors.lastname: Rohrberg
authors.forename: Helle
authors.initials: H
authors.lastname: Pappot
authors.forename: Ulrik
authors.initials: U
authors.lastname: Lassen
authors.forename: Maj
authors.initials: M
authors.lastname: Westman
authors.forename: René K
authors.initials: RK
authors.lastname: Olesen
authors.forename: Per
authors.initials: P
authors.lastname: Pfeiffer
authors.forename: Morten
authors.initials: M
authors.lastname: Ladekarl
authors.forename: Morten
authors.initials: M
authors.lastname: Sørensen
authors.forename: Ib J
authors.initials: IJ
authors.lastname: Christensen
authors.forename: Birgit G
authors.initials: BG
authors.lastname: Skov
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000068258:Bevacizumab; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism; D000069347:Erlotinib Hydrochloride; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D011799:Quinazolines / Q000627:therapeutic use*; D016019:Survival Analysis; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D018631:ras Proteins / Q000235:genetics
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D011799:Quinazolines; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D040301:Vascular Endothelial Growth Factor Receptor-2; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins