Research Papers:

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)

Loic Lebellec, François Bertucci, Emmanuelle Tresch-Bruneel, Emmanuelle Bompas, Yves Toiron, Luc Camoin, Olivier Mir, Valerie Laurence, Stephanie Clisant, Emilie Decoupigny, Jean-Yves Blay, Anthony Goncalves and Nicolas Penel _

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Oncotarget. 2016; 7:73984-73994. https://doi.org/10.18632/oncotarget.12172

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Loic Lebellec1, François Bertucci2, Emmanuelle Tresch-Bruneel3, Emmanuelle Bompas4, Yves Toiron5, Luc Camoin5, Olivier Mir6, Valerie Laurence7, Stephanie Clisant8,3, Emilie Decoupigny8, Jean-Yves Blay9, Anthony Goncalves5, Nicolas Penel1,3

1Department of Medical Oncology, Centre Oscar Lambret, Lille, France

2Department of Medical Oncology, Institut Paoli-Calmette, Marseille, France

3SIRIC OncoLille, Clinical Research and Methodological Platform, Lille, France

4Department of Medical Oncology, Centre René Gauducheau, Nantes, France

5Department of Molecular Pharmacology, Cancer Research Center of Marseille, Institut Paoli Calmettes, Marseille, France

6Department of Medical Oncology, Gustave Roussy, Villejuif, France

7Department of Medical Oncology, Institut Curie, Paris, France

8Clinical Research Unit, Centre Oscar Lambret, Lille, France

9Department of Medical Oncology, Centre Léon Bérard, Lyon, France

Correspondence to:

Nicolas Penel, email: [email protected]

Keywords: chordoma, sorafenib, biomarker, placental growth factor, vascular endothelial growth factor

Received: March 31, 2016     Accepted: September 13, 2016     Published: September 21, 2016


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.

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