Prognostic and predictive value of VEGF, sVEGFR-2 and CEA in mCRC studies comparing cediranib, bevacizumab and chemotherapy

Br J Cancer. 2013 Apr 2;108(6):1316-23. doi: 10.1038/bjc.2013.79. Epub 2013 Feb 28.


Background: The prognostic/predictive value of potential vascular endothelial growth factor (VEGF) signalling biomarkers was evaluated retrospectively using samples from two randomized Phase III studies (HORIZON II and III) investigating cediranib in metastatic colorectal cancer (mCRC).

Methods: Baseline levels of VEGF, soluble VEGF receptor-2 (sVEGFR-2) and carcinoembryonic antigen (CEA) were measured in plasma/serum samples collected from patients participating in HORIZON II (n=860; FOLFOX/XELOX plus cediranib 20 mg (n=502) or placebo (n=358)) and HORIZON III (n=1422; mFOLFOX6 plus cediranib 20 mg (n=709) or bevacizumab (n=713)). Median biomarker baseline levels determined cutoff values for the patient subgroups.

Results: Baseline data were available for 88-97% of patients/study (>2000 patients). In both the studies, high baseline VEGF and CEA were associated with worse outcomes for progression-free survival (PFS) and overall survival (OS) independent of treatment (HORIZON II OS: VEGF, hazard ratio (HR)=1.35 (95% confidence interval (CI): 1.12-1.63); CEA, HR=1.63 (1.36-1.96); HORIZON III OS: VEGF, HR=1.32 (1.12-1.54); CEA, HR=1.50 (1.29-1.76)). sVEGFR-2 was not prognostic for PFS/OS. Baseline VEGF and CEA were not predictive for PFS/OS outcome to cediranib treatment; low sVEGFR-2 was associated with a trend towards improved cediranib effect in HORIZON II.

Conclusion: Baseline VEGF and CEA levels were treatment-independent prognostic biomarkers for PFS and OS in both the studies.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bevacizumab
  • Biomarkers, Tumor / blood
  • Carcinoembryonic Antigen / blood*
  • Colorectal Neoplasms / blood
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / mortality*
  • Enzyme-Linked Immunosorbent Assay
  • Follow-Up Studies
  • Humans
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Prognosis
  • Quinazolines / administration & dosage
  • Retrospective Studies
  • Survival Rate
  • Vascular Endothelial Growth Factor A / blood*
  • Vascular Endothelial Growth Factor Receptor-2 / blood*


  • Antibodies, Monoclonal, Humanized
  • Biomarkers, Tumor
  • Carcinoembryonic Antigen
  • Quinazolines
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Bevacizumab
  • Vascular Endothelial Growth Factor Receptor-2
  • cediranib