title: Evaluation of Angiopoietin-2 as a biomarker in gastric cancer: results from the randomised phase III AVAGAST trial.
abstract: BACKGROUND
  In the phase III AVAGAST trial, the addition of bevacizumab to chemotherapy improved progression-free survival (PFS) but not overall survival (OS) in patients with advanced gastric cancer. We studied the role of Angiopoietin-2 (Ang-2), a key driver of tumour angiogenesis, metastasis and resistance to antiangiogenic treatment, as a biomarker.
  
  
  METHODS
  Previously untreated, advanced gastric cancer patients were randomly assigned to receive bevacizumab (n=387) or placebo (n=387) in combination with chemotherapy. Plasma collected at baseline and at progression was analysed by ELISA. The role of Ang-2 as a prognostic and a predictive biomarker of bevacizumab efficacy was studied using a Cox proportional hazards model. Logistic regression analysis was applied for correlations with metastasis.
  
  
  RESULTS
  Median baseline plasma Ang-2 levels were lower in Asian (2143 pg ml(-1)) vs non-Asian patients (3193 pg ml(-1)), P<0.0001. Baseline plasma Ang-2 was identified as an independent prognostic marker for OS but did not predict bevacizumab efficacy alone or in combination with baseline VEGF. Baseline plasma Ang-2 correlated with the frequency of liver metastasis (LM) at any time: Odds ratio per 1000 pg ml(-1) increase: 1.19; 95% CI 1.10-1.29; P<0.0001 (non-Asians) and 1.37; 95% CI 1.13-1.64; P=0.0010 (Asians).
  
  
  CONCLUSIONS
  Baseline plasma Ang-2 is a novel prognostic biomarker for OS in advanced gastric cancer strongly associated with LM. Differences in Ang-2 mediated vascular response may, in part, account for outcome differences between Asian and non-Asian patients; however, data have to be further validated. Ang-2 is a promising drug target in gastric cancer.
authors.affiliation: University Cancer Center Leipzig (UCCL), University Hospital Leipzig, Liebigstr. 20, Leipzig 04103, Germany.
authors.forename: Ulrich T
authors.initials: UT
authors.lastname: Hacker
authors.affiliation: Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.
authors.forename: Laura
authors.initials: L
authors.lastname: Escalona-Espinosa
authors.affiliation: Biostatistics F. Hoffman-La Roche AG, Basel, Switzerland.
authors.forename: Nicola
authors.initials: N
authors.lastname: Consalvo
authors.affiliation: Department of Internal Medicine I, University Hospital Cologne, Cologne, Germany.|Center of Integrated Oncology (CIO) Cologne-Bonn, Cologne, Germany.
authors.forename: Valentin
authors.initials: V
authors.lastname: Goede
authors.affiliation: Center of Integrated Oncology (CIO) Cologne-Bonn, Cologne, Germany.|Department of General, Visceral and Cancer Surgery, University Hospital Cologne, Cologne, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Schiffmann
authors.affiliation: University of Wuerzburg, PCI, Biocenter, Am Hubland, Wuerzburg 97074, Germany.
authors.forename: Stefan J
authors.initials: SJ
authors.lastname: Scherer
authors.affiliation: Oncology Early Clinical Developement, Genentech, Inc., South San Francisco, CA, USA.
authors.forename: Priti
authors.initials: P
authors.lastname: Hedge
authors.affiliation: University Hospital Gasthuisberg Leuven and KU Leuven, Leuven, Belgium.
authors.forename: Eric
authors.initials: E
authors.lastname: Van Cutsem
authors.affiliation: Department of Internal Medicine I, University Hospital Cologne, Cologne, Germany.|Center of Integrated Oncology (CIO) Cologne-Bonn, Cologne, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Coutelle
authors.affiliation: Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.|Hannover Medical School, Institute of Experimental Hematology, Hannover, Germany.
authors.forename: Hildegard
authors.initials: H
authors.lastname: Büning
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000068258:Bevacizumab / Q000008:administration & dosage; D014408:Biomarkers, Tumor / Q000097:blood*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000175:diagnosis; D011379:Prognosis; D013274:Stomach Neoplasms / Q000097:blood* / Q000175:diagnosis* / Q000188:drug therapy; D033921:Vesicular Transport Proteins / Q000097:blood*
chemical_list: D020533:Angiogenesis Inhibitors; D014408:Biomarkers, Tumor; C555023:VPS51 protein, human; D033921:Vesicular Transport Proteins; D000068258:Bevacizumab