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. 2018 Oct 11;18(1):963. doi: 10.1186/s12885-018-4828-1.

Abstract

Background: We report here a correlation analysis conducted along with a phase II trial assessing bevacizumab in combination with weekly paclitaxel.

Methods: 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.

Results: 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.

Conclusions: 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).

Keywords: Angiosarcoma; Bevacizumab; Biomarkers; Radiation-induced angiosarcoma; Weekly paclitaxel.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Phytogenic / administration & dosage*
  • Bevacizumab / administration & dosage*
  • Biomarkers, Tumor* / blood
  • Female
  • Hemangiosarcoma / blood
  • Hemangiosarcoma / drug therapy*
  • Hemangiosarcoma / physiopathology
  • Humans
  • Middle Aged
  • Paclitaxel / administration & dosage*
  • Placenta Growth Factor / blood
  • Prognosis
  • Vascular Endothelial Growth Factor A / blood

Substances

  • Antineoplastic Agents, Phytogenic
  • Biomarkers, Tumor
  • PGF protein, human
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Placenta Growth Factor
  • Bevacizumab
  • Paclitaxel

Associated data

  • ClinicalTrials.gov/NCT01303497