Prognostic and predictive factors for angiosarcoma patients receiving paclitaxel once weekly plus or minus bevacizumab: an ancillary study derived from a randomized clinical trial.
BMC cancer, Oct 2018
Lebellec L, Bertucci F, Tresch-Bruneel E, Ray-Coquard I, Le Cesne A, Bompas E, Blay JY, Italiano A, Mir O, Ryckewaert T, Toiron Y, Camoin L, Goncalves A, Penel N, Le Deley MC.
We report here a correlation analysis conducted along with a phase II trial assessing bevacizumab in combination with weekly paclitaxel.
Circulating pro/anti-angiogenic factors were assessed on day 1 (D1) and day 8 (D8). The prognostic value for progression-free survival (PFS) was evaluated using a Cox model with biomarkers as continuous variables.
Among the 51 patients enrolled and treated in this trial, biomarker analysis was performed for 42: 18 in Arm A (single-agent) and 24 in Arm B (combination). With a median follow-up of 46 months, PFS was 5.5 versus 5.7 months, respectively (p = 0.75). According to univariate analysis, factors associated with a poor PFS were as follows: visceral angiosarcoma, de novo angiosarcoma, and high PlGF and low VEGF-C baseline values. In multivariate analysis, de novo angiosarcoma (HR = 2.5; p = 0.024) and baseline VEGF-C value (HR = 0.7; p = 0.003) were significant prognostic factors. We observed a significant increase in circulating PlGF (< 0.001) and a decrease in VEGF (< 0.001) during bevacizumab treatment. An increase in FGF was associated with a poor outcome.
De novo angiosarcoma and a low baseline level of VEGF-C were found to be associated with a poor prognosis. Addition of bevacizumab induces major changes in circulating biomarkers (VEGF and PlGF) in a short timeframe without impacting PFS.
TRIAL REGISTRATION :
Retrospectively registered on EudraCT N° 2009-017020-59 and NCT01303497 (February 24, 2011).
Angiosarcoma; Bevacizumab; Biomarkers; Radiation-induced angiosarcoma; Weekly paclitaxel