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).
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.
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.
High levels of VEGF at D1 and D7 were associated with poor outcome in advanced chordoma receiving sorafenib.
Clinical trial identification
Legal entity responsible for the study
Centre Oscar Lambret
Institut National du Cancer (PHRC-2009/Grant) and Bayer HealthCare France.
All authors have declared no conflicts of interest.