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Prognostic and predictive value of VEGF, sVEGFR-2 and CEA in mCRC studies comparing cediranib, bevacizumab and chemotherapy

BACKGROUND: The prognostic/predictive value of potential vascular endothelial growth factor (VEGF) signalling biomarkers was evaluated retrospectively using samples from two randomized Phase III studies (HORIZON II and III) investigating cediranib in metastatic colorectal cancer (mCRC). METHODS: Bas...

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Autores principales: Jürgensmeier, J M, Schmoll, H-J, Robertson, J D, Brooks, L, Taboada, M, Morgan, S R, Wilson, D, Hoff, P M
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3619270/
https://www.ncbi.nlm.nih.gov/pubmed/23449351
http://dx.doi.org/10.1038/bjc.2013.79
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author Jürgensmeier, J M
Schmoll, H-J
Robertson, J D
Brooks, L
Taboada, M
Morgan, S R
Wilson, D
Hoff, P M
author_facet Jürgensmeier, J M
Schmoll, H-J
Robertson, J D
Brooks, L
Taboada, M
Morgan, S R
Wilson, D
Hoff, P M
author_sort Jürgensmeier, J M
collection PubMed
description BACKGROUND: The prognostic/predictive value of potential vascular endothelial growth factor (VEGF) signalling biomarkers was evaluated retrospectively using samples from two randomized Phase III studies (HORIZON II and III) investigating cediranib in metastatic colorectal cancer (mCRC). METHODS: Baseline levels of VEGF, soluble VEGF receptor-2 (sVEGFR-2) and carcinoembryonic antigen (CEA) were measured in plasma/serum samples collected from patients participating in HORIZON II (n=860; FOLFOX/XELOX plus cediranib 20 mg (n=502) or placebo (n=358)) and HORIZON III (n=1422; mFOLFOX6 plus cediranib 20 mg (n=709) or bevacizumab (n=713)). Median biomarker baseline levels determined cutoff values for the patient subgroups. RESULTS: Baseline data were available for 88–97% of patients/study (>2000 patients). In both the studies, high baseline VEGF and CEA were associated with worse outcomes for progression-free survival (PFS) and overall survival (OS) independent of treatment (HORIZON II OS: VEGF, hazard ratio (HR)=1.35 (95% confidence interval (CI): 1.12–1.63); CEA, HR=1.63 (1.36–1.96); HORIZON III OS: VEGF, HR=1.32 (1.12–1.54); CEA, HR=1.50 (1.29–1.76)). sVEGFR-2 was not prognostic for PFS/OS. Baseline VEGF and CEA were not predictive for PFS/OS outcome to cediranib treatment; low sVEGFR-2 was associated with a trend towards improved cediranib effect in HORIZON II. CONCLUSION: Baseline VEGF and CEA levels were treatment-independent prognostic biomarkers for PFS and OS in both the studies.
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spelling pubmed-36192702014-04-02 Prognostic and predictive value of VEGF, sVEGFR-2 and CEA in mCRC studies comparing cediranib, bevacizumab and chemotherapy Jürgensmeier, J M Schmoll, H-J Robertson, J D Brooks, L Taboada, M Morgan, S R Wilson, D Hoff, P M Br J Cancer Molecular Diagnostics BACKGROUND: The prognostic/predictive value of potential vascular endothelial growth factor (VEGF) signalling biomarkers was evaluated retrospectively using samples from two randomized Phase III studies (HORIZON II and III) investigating cediranib in metastatic colorectal cancer (mCRC). METHODS: Baseline levels of VEGF, soluble VEGF receptor-2 (sVEGFR-2) and carcinoembryonic antigen (CEA) were measured in plasma/serum samples collected from patients participating in HORIZON II (n=860; FOLFOX/XELOX plus cediranib 20 mg (n=502) or placebo (n=358)) and HORIZON III (n=1422; mFOLFOX6 plus cediranib 20 mg (n=709) or bevacizumab (n=713)). Median biomarker baseline levels determined cutoff values for the patient subgroups. RESULTS: Baseline data were available for 88–97% of patients/study (>2000 patients). In both the studies, high baseline VEGF and CEA were associated with worse outcomes for progression-free survival (PFS) and overall survival (OS) independent of treatment (HORIZON II OS: VEGF, hazard ratio (HR)=1.35 (95% confidence interval (CI): 1.12–1.63); CEA, HR=1.63 (1.36–1.96); HORIZON III OS: VEGF, HR=1.32 (1.12–1.54); CEA, HR=1.50 (1.29–1.76)). sVEGFR-2 was not prognostic for PFS/OS. Baseline VEGF and CEA were not predictive for PFS/OS outcome to cediranib treatment; low sVEGFR-2 was associated with a trend towards improved cediranib effect in HORIZON II. CONCLUSION: Baseline VEGF and CEA levels were treatment-independent prognostic biomarkers for PFS and OS in both the studies. Nature Publishing Group 2013-04-02 2013-02-28 /pmc/articles/PMC3619270/ /pubmed/23449351 http://dx.doi.org/10.1038/bjc.2013.79 Text en Copyright © 2013 Cancer Research UK http://creativecommons.org/licenses/by-nc-sa/3.0/ From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
spellingShingle Molecular Diagnostics
Jürgensmeier, J M
Schmoll, H-J
Robertson, J D
Brooks, L
Taboada, M
Morgan, S R
Wilson, D
Hoff, P M
Prognostic and predictive value of VEGF, sVEGFR-2 and CEA in mCRC studies comparing cediranib, bevacizumab and chemotherapy
title Prognostic and predictive value of VEGF, sVEGFR-2 and CEA in mCRC studies comparing cediranib, bevacizumab and chemotherapy
title_full Prognostic and predictive value of VEGF, sVEGFR-2 and CEA in mCRC studies comparing cediranib, bevacizumab and chemotherapy
title_fullStr Prognostic and predictive value of VEGF, sVEGFR-2 and CEA in mCRC studies comparing cediranib, bevacizumab and chemotherapy
title_full_unstemmed Prognostic and predictive value of VEGF, sVEGFR-2 and CEA in mCRC studies comparing cediranib, bevacizumab and chemotherapy
title_short Prognostic and predictive value of VEGF, sVEGFR-2 and CEA in mCRC studies comparing cediranib, bevacizumab and chemotherapy
title_sort prognostic and predictive value of vegf, svegfr-2 and cea in mcrc studies comparing cediranib, bevacizumab and chemotherapy
topic Molecular Diagnostics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3619270/
https://www.ncbi.nlm.nih.gov/pubmed/23449351
http://dx.doi.org/10.1038/bjc.2013.79
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