Circulating vascular endothelial growth factor (VEGF) as predictive factor of progression-free survival in patients with advanced chordoma receiving sorafenib: an analysis from a phase II trial of the french sarcoma group (GSF/GETO)

Oncotarget. 2016 Nov 8;7(45):73984-73994. doi: 10.18632/oncotarget.12172.

Abstract

Background: Patients with advanced chordoma are often treated with tyrosine kinase inhibitors without any predictive factor to guide decision. We report herein an ancillary analysis of the the Angionext phase II trial (NCT 00874874).

Results: From May 2011 to January 2014, 26 were sampled. The 9-month PFS rate was 72.9% (95%-CI: 45.9-87.9). During sorafenib treatment, a significant increase in PlGF (18.4 vs 43.8 pg/mL, p<0.001) was noted along with a non-significant increase in VEGF (0.7 vs 1.0 ng/mL, p=0.07). VEGF at D1 >1.04 ng/mL (HR=12.5, 95%-CI: 1.37-114, p=0.025) and VEGF at D7 >1.36 ng/mL (HR=10.7, 95%-CI: 1.16-98, p=0.037) were associated with shorter PFS. The 9-month PFS rate was 92.3% (95%-CI: 56.6-98.9) when VEGF at D1 was ≤1.04 ng/mL versus 23.3% (95%-CI: 1.0-63.2) when >1.04 ng/mL.

Patients and methods: Chordoma patients were treated with sorafenib 800 mg/day for 9 months, unless earlier occurrence of progression or toxicities. Six biomarkers (sE-Selectin, VEGF, VEGF-C, placental growth factor (PlGF), Thrombospondin, Stem Cell Factor (SCF)) were measured at baseline (day 1: D1) and day 7 (D7).

Conclusion: High levels of VEGF was associated with poor outcome.

Keywords: biomarker; chordoma; placental growth factor; sorafenib; vascular endothelial growth factor.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor
  • Chordoma / blood*
  • Chordoma / drug therapy
  • Chordoma / mortality*
  • Chordoma / pathology
  • Clinical Trials, Phase II as Topic
  • Combined Modality Therapy
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Membrane Proteins / blood
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Niacinamide / analogs & derivatives
  • Niacinamide / therapeutic use
  • Phenylurea Compounds / therapeutic use
  • Prognosis
  • Protein Kinase Inhibitors / therapeutic use
  • Sorafenib
  • Vascular Endothelial Growth Factor A / blood*

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Membrane Proteins
  • PIGF protein, human
  • Phenylurea Compounds
  • Protein Kinase Inhibitors
  • Vascular Endothelial Growth Factor A
  • Niacinamide
  • Sorafenib