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 1 François Bertucci 2 Emmanuelle Tresch-Bruneel 3 Isabelle Ray-Coquard 4 Axel Le Cesne 5 Emmanuelle Bompas 6 Jean-Yves Blay 4 Antoine Italiano 7 Olivier Mir 5 Thomas Ryckewaert 7 Yves Toiron 8 Luc Camoin 8 Anthony Gonçalves 2 Nicolas Penel 1, 3, * Marie-Cécile Le Deley 9, 3, 10
* Corresponding author
1 Ecole de Médecine [CHRU Lille]
2 Département d’Oncologie Médicale [CRCM, Marseille]
3 Centre Oscar Lambret - Direction de la recherche et de l'innovation [Lille]
4 Centre Léon Bérard - Département d'Oncologie Médicale [Lyon]
5 Sarcome
Département de médecine oncologique [Gustave Roussy]
6 Département d'oncologie médicale [ICO, Saint Herblain]
7 Département d'oncologie médicale
8 Institut Paoli-Calmettes
9 UP11 - Université Paris-Sud - Paris 11
10 SBE - Service de biostatistique et d'épidémiologie
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
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Loïc Lebellec, François Bertucci, Emmanuelle Tresch-Bruneel, Isabelle Ray-Coquard, Axel Le Cesne, et al.. 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, BioMed Central, 2018, 18 (1), pp.963. ⟨10.1186/s12885-018-4828-1⟩. ⟨inserm-02050851⟩

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