title: Prognostic and predictive value of VEGF, sVEGFR-2 and CEA in mCRC studies comparing cediranib, bevacizumab and chemotherapy.
abstract: 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.
  
  
  CONCLUSIONS
  Baseline VEGF and CEA levels were treatment-independent prognostic biomarkers for PFS and OS in both the studies.
authors: Translational Sciences, Oncology, AstraZeneca, Alderley Park, Macclesfield SK10 4TG, UK. juliane.jurgensmeier@astrazeneca.com
authors: J M
authors: JM
authors: Jürgensmeier
authors: H-J
authors: HJ
authors: Schmoll
authors: J D
authors: JD
authors: Robertson
authors: L
authors: L
authors: Brooks
authors: M
authors: M
authors: Taboada
authors: S R
authors: SR
authors: Morgan
authors: D
authors: D
authors: Wilson
authors: P M
authors: PM
authors: Hoff
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D014408:Biomarkers, Tumor / Q000097:blood; D002272:Carcinoembryonic Antigen / Q000097:blood*; D015179:Colorectal Neoplasms / Q000097:blood / Q000188:drug therapy / Q000401:mortality*; D004797:Enzyme-Linked Immunosorbent Assay; D005500:Follow-Up Studies; D006801:Humans; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D011799:Quinazolines / Q000008:administration & dosage; D012189:Retrospective Studies; D015996:Survival Rate; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000097:blood*; D007211:Indoles
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D011799:Quinazolines; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2; C467484:VEGFA protein, human; C500926:cediranib; D007211:Indoles