Prognostic and predictive factors for angiosarcoma patients receiving paclitaxel once weekly plus or minus bevacizumab: an ancillary study derived from a randomized clinical trial

Loïc Lebellec, François Bertucci, Emmanuelle Tresch-Bruneel, Isabelle Ray-Coquard, Axel Le Cesne, Emmanuelle Bompas, Jean-Yves Blay, Antoine Italiano, Olivier Mir, Thomas Ryckewaert, Yves Toiron, Luc Camoin, Anthony Goncalves, Nicolas Penel, Marie-Cécile Le Deley, Loïc Lebellec, François Bertucci, Emmanuelle Tresch-Bruneel, Isabelle Ray-Coquard, Axel Le Cesne, Emmanuelle Bompas, Jean-Yves Blay, Antoine Italiano, Olivier Mir, Thomas Ryckewaert, Yves Toiron, Luc Camoin, Anthony Goncalves, Nicolas Penel, Marie-Cécile Le Deley

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.

Conflict of interest statement

Ethics approval and consent to participate

Study investigations were conducted after approval by the local Ethics Committee (Nord-Ouest IV Commit de Protection des Patients) on 9th March, 2010, and after the approval of the French Health Authority (AFSSAPS) on 12th April, 2010. Signed informed consent was obtained from each patient. The study was registered in the European Clinical Trials Register (EudraCT N° 2009–017020-59) and in the US Clinical Trials Register (NCT01303497) and was conducted in agreement with the Declaration of Helsinki and International Conference on Harmonization of Good Clinical Practice guidelines.

Consent for publication

Not applicable

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
a PFS according to treatment arm. b PFS according to tumor location. c PFS according to radiation-induced or de novo sarcoma
Fig. 2
Fig. 2
Variation (D8 – D1) in biomarker values in each treatment arm

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