Weekly paclitaxel (WP) +/- bevacizumab (B) in angiosarcoma (AS) patients (pts): Analysis of prognostic/predictive factors from a randomized phase 2 trial.

Abstract

11024 Background: WP is an active regimen for treatment of AS pts (Ray-Coquard JCO 2015). We report here the correlative analysis conducted during a phase 2 trial assessing WP +/- B. Methods: Circulating pro/anti-angiogenic factors (FGF, PlGF, SCF, Selectin, thrombospondin, VEGF, VEGF-C) were collected at D1 and D8. Prognostic value for PFS was assessed using Cox model (biomarkers as continuous variables). We attempt to identify subgroups of pts benefiting from adding B using interaction tests (predictive factors). Results: Among the 51 pts enrolled in this trial, 45 were analyzable: 20 in Arm A (WP without B) and 25 in Arm B (with B). Median PFS was 5.5 and 6.1 months, respectively (p = 0.84). Samples were collected in 45 pts at D1 and 42 pts at D1 and 8. Baseline biomarkers were similar in both arms (excluding Selectin, significantly lower in arm A: median of 25 vs. 35 ng/mL, p = 0.03). In arm A, there was no significant difference between values at D1 and D8. In arm B, there were a significant decrease in VEGF (from a median of 0.49 to 0.08 ng/mL; p < 0.01) and selectin (from a median of 35.3 to 31.7 ng/mL; p < 0.01), and a significant increase in PlGF (from a median of 16.1 to 30.0 pg/mL; p < 0.01). In univariate analysis, factors associated with PFS were: de novo vs. radiation-induced AS (HR = 2.39 (p < 0.01), visceral vs. superficial AS (HR = 2.04; p < 0.03), VEGF-C at D1 (HR = 0.77; p < 0.03), FGF at D8 (HR = 1.17; p < 0.01), difference in FGF D8-D1 (HR = 1.24; p < 0.01), and PlGF value at D1 (HR = 1.02; p < 0.05). In multivariate analysis, factors associated with PFS were: de novo AS (HR = 2.39; p = 0.03), VEGF-C at D1 (HR = 0.73; p < 0.02) and FGF difference between D8 and D1 (HR = 1.16; p < 0.02). None of these factors were associated with benefit of adding B. Conclusions: Baseline VEGF-C levels and change in FGF were independent prognostic factors in pts with or without B. Addition of B significantly decreased the level of circulating VEGF and selectin and increased the level of circulating PlGF in AS patients. We did not identify subgroup of pts benefiting from adding of B to WP. Clinical trial information: NCT01303497.