1405PD - Circulating vascular endothelial growth factor (VEGF) as prognostic factor of progression-free survival in patients with advanced chordoma receivin...

Date 10 October 2016
Event ESMO 2016 Congress
Session Sarcoma
Topics Sarcoma
Presenter Loïc Lebellec
Citation Annals of Oncology (2016) 27 (6): 483-492. 10.1093/annonc/mdw388
Authors L. Lebellec1, F. Bertucci2, E. Tresch-Bruneel3, E. Bompas4, Y. Toiron5, L. Camoin5, O. Mir6, V. Laurence7, S. Clisant8, E. Decoupigny3, J. Blay9, A. Gonçalves2, N. Penel1
  • 1Medical Oncology, Centre Oscar Lambret, 59020 - Lille/FR
  • 2Oncologie Médicale, Institute Paoli Calmettes, 13274 - Marseille/FR
  • 3Clinical Research And Methodological Platform, Centre Oscar Lambret, 59020 - Lille/FR
  • 4Department Of Medical Oncology, Institut de cancérologie de l'Ouest - René Gauducheau, 44805 - Saint-Herblain/FR
  • 5Department Of Molecular Pharmacology, Institute Paoli Calmettes, 13009 - Marseille/FR
  • 6Department Of Medical Oncology, Institut Gustave Roussy, 94805 - Villejuif/FR
  • 7Medical Oncology, Institut Curie, 75005 - Paris/FR
  • 8Clinical Research Unit, Centre Oscar Lambret, 59020 - Lille/FR
  • 9Medical Oncology, Centre Léon Bérard, 69008 - Lyon/FR

Abstract

Background

Patients with advanced chordoma are often treated with tyrosine kinase inhibitors without any predictive factor to guide decision. We report herein the ancillary analysis of the predictive values of circulating pro/antiangiogenic biomarkers among patients included in the Angionext phase II trial and treated with sorafenib (NCT 00874874).

Methods

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 in 2 blood samples at baseline (day 1: D1) and day 7 (D7). Changes in levels of circulating biomarkers were analyzed with paired Student t-test. Prognostic value of biomarkers for progression-free survival (PFS) was analyzed using univariate Cox model.

Results

From May 2011 to January 2014, 26 out of 27 patients included in the original study were sampled, including 17 men and 9 women, with a median age of 64 years. The primary sites were sacrum (20, 78%), mobile spine and skull base (3 each, 11%). 50% of patients had metastatic disease (13/26). After central radiological review, 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 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. The 9-month PFS rates was 91.7% (95%-CI: 53.9-98.8) when VEGF at D7 was ≤1.36 ng/mL versus 27.8% (95%-CI: 1.3-68.4) when >1.36 ng/mL. The serum levels of five other biomarkers were not associated with PFS.

Conclusions

High levels of VEGF at D1 and D7 were associated with poor outcome in advanced chordoma receiving sorafenib.

Clinical trial identification

NCT00874874

Legal entity responsible for the study

Centre Oscar Lambret

Funding

Institut National du Cancer (PHRC-2009/Grant) and Bayer HealthCare France.

Disclosure

All authors have declared no conflicts of interest.