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Circulating vascular endothelial growth factor (VEGF) as prognostic 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)

Date

10 Oct 2016

Session

Sarcoma

Presenters

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

Author affiliations

  • 1 Medical Oncology, Centre Oscar Lambret, 59020 - Lille/FR
  • 2 Oncologie Médicale, Institute Paoli Calmettes, 13274 - Marseille/FR
  • 3 Clinical Research And Methodological Platform, Centre Oscar Lambret, 59020 - Lille/FR
  • 4 Department Of Medical Oncology, Institut de cancérologie de l'Ouest - René Gauducheau, 44805 - Saint-Herblain/FR
  • 5 Department Of Molecular Pharmacology, Institute Paoli Calmettes, 13009 - Marseille/FR
  • 6 Department Of Medical Oncology, Institut Gustave Roussy, 94805 - Villejuif/FR
  • 7 Medical Oncology, Institut Curie, 75005 - Paris/FR
  • 8 Clinical Research Unit, Centre Oscar Lambret, 59020 - Lille/FR
  • 9 Medical Oncology, Centre Léon Bérard, 69008 - Lyon/FR
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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.

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