Association of circulating VEGF-A levels with outcome in patients with vascular sarcomas receiving sorafenib (Sor): Exploratory analysis from AngioNext study.

Abstract

10525 Background: We have carried out a stratified phase II study of Sor in pts with advanced angiosarcoma (AA, n=32), malignant solitary tumour (SFT, n=4) & epithelioid hemangioendothelioma (EE, n=13). We report here the correlative analysis of predictive value of circulating pro/anti-angiogenetic biomarkers. Methods: Using ELISA method (R&D SYSTEMS) Circulating biomarkers (VEGF-A [pg/mL], Thrombospondin-1 (TSP1) [µg/mL], Stem Cell Factor (SCF) [pg/mL], Placental growth factor (PlGF) [pg/mL], VEGF-C [pg/mL] & E-selectin [ng/mL]) have been measured before Sor treatment & after 7 days. We analyze the correlation with histological subtypes, presence of metastases, best response and occurrence of hemorrhage and Gr3-4 arterial hypertension. Results: VEGF-A (mean value 475 vs 541 pg/mL, p=0.002), TSP1 (16 vs 24 µg/mL, p=0.0002), PlGF (20.9 vs 40.7 pg/mL, p=0.0001) significantly increased during the treatment. Sor treatment did not affect the levels of SCF, VEGF-C & E-selectin. The distributions of all biomarkers were similar across the histological subtypes, whatever the presence of metastasis, the occurrence of hemorrhage or arterial hypertension. 2 biomarkers were associated with better outcome:VEGF-A & PlGF. Best objective response and non-progression at 180 days were associated with low level of VEGF-A at baseline (p=0.04 and p= 0,03 respectively). There was a correlation between circulating level of VEGF-A & time to progression (TTP) (r=-0.47, p=0.001). Best objective response and non-progression at 180 days were not associated with baseline level of PlIGF (p=0.34 and 0.07), but there was a correlation between circulating level of PlIGF at baseline and TTP (-0.31, p=0.02). Conclusions: In pts with vascular sarcomas receiving Sor, we have observed a significant decrease in circulating level of VEGF-A. Low level of VEGF-A at baseline (<500 pg/mL) was significantly associated with better outcome, especially best objective response rate, non-progression at 180 days and time to progression. Clinical trial information: 2007-004651-10.