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

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) w...

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Autores principales: Lebellec, Loïc, Bertucci, François, Tresch-Bruneel, Emmanuelle, Ray-Coquard, Isabelle, Le Cesne, Axel, Bompas, Emmanuelle, Blay, Jean-Yves, Italiano, Antoine, Mir, Olivier, Ryckewaert, Thomas, Toiron, Yves, Camoin, Luc, Goncalves, Anthony, Penel, Nicolas, Le Deley, Marie-Cécile
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6180490/
https://www.ncbi.nlm.nih.gov/pubmed/30305054
http://dx.doi.org/10.1186/s12885-018-4828-1
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author Lebellec, Loïc
Bertucci, François
Tresch-Bruneel, Emmanuelle
Ray-Coquard, Isabelle
Le Cesne, Axel
Bompas, Emmanuelle
Blay, Jean-Yves
Italiano, Antoine
Mir, Olivier
Ryckewaert, Thomas
Toiron, Yves
Camoin, Luc
Goncalves, Anthony
Penel, Nicolas
Le Deley, Marie-Cécile
author_facet Lebellec, Loïc
Bertucci, François
Tresch-Bruneel, Emmanuelle
Ray-Coquard, Isabelle
Le Cesne, Axel
Bompas, Emmanuelle
Blay, Jean-Yves
Italiano, Antoine
Mir, Olivier
Ryckewaert, Thomas
Toiron, Yves
Camoin, Luc
Goncalves, Anthony
Penel, Nicolas
Le Deley, Marie-Cécile
author_sort Lebellec, Loïc
collection PubMed
description 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). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12885-018-4828-1) contains supplementary material, which is available to authorized users.
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spelling pubmed-61804902018-10-18 Prognostic and predictive factors for angiosarcoma patients receiving paclitaxel once weekly plus or minus bevacizumab: an ancillary study derived from a randomized clinical trial Lebellec, Loïc Bertucci, François Tresch-Bruneel, Emmanuelle Ray-Coquard, Isabelle Le Cesne, Axel Bompas, Emmanuelle Blay, Jean-Yves Italiano, Antoine Mir, Olivier Ryckewaert, Thomas Toiron, Yves Camoin, Luc Goncalves, Anthony Penel, Nicolas Le Deley, Marie-Cécile BMC Cancer Research Article 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). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12885-018-4828-1) contains supplementary material, which is available to authorized users. BioMed Central 2018-10-11 /pmc/articles/PMC6180490/ /pubmed/30305054 http://dx.doi.org/10.1186/s12885-018-4828-1 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Lebellec, Loïc
Bertucci, François
Tresch-Bruneel, Emmanuelle
Ray-Coquard, Isabelle
Le Cesne, Axel
Bompas, Emmanuelle
Blay, Jean-Yves
Italiano, Antoine
Mir, Olivier
Ryckewaert, Thomas
Toiron, Yves
Camoin, Luc
Goncalves, Anthony
Penel, Nicolas
Le Deley, Marie-Cécile
Prognostic and predictive factors for angiosarcoma patients receiving paclitaxel once weekly plus or minus bevacizumab: an ancillary study derived from a randomized clinical trial
title Prognostic and predictive factors for angiosarcoma patients receiving paclitaxel once weekly plus or minus bevacizumab: an ancillary study derived from a randomized clinical trial
title_full Prognostic and predictive factors for angiosarcoma patients receiving paclitaxel once weekly plus or minus bevacizumab: an ancillary study derived from a randomized clinical trial
title_fullStr Prognostic and predictive factors for angiosarcoma patients receiving paclitaxel once weekly plus or minus bevacizumab: an ancillary study derived from a randomized clinical trial
title_full_unstemmed Prognostic and predictive factors for angiosarcoma patients receiving paclitaxel once weekly plus or minus bevacizumab: an ancillary study derived from a randomized clinical trial
title_short Prognostic and predictive factors for angiosarcoma patients receiving paclitaxel once weekly plus or minus bevacizumab: an ancillary study derived from a randomized clinical trial
title_sort prognostic and predictive factors for angiosarcoma patients receiving paclitaxel once weekly plus or minus bevacizumab: an ancillary study derived from a randomized clinical trial
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6180490/
https://www.ncbi.nlm.nih.gov/pubmed/30305054
http://dx.doi.org/10.1186/s12885-018-4828-1
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