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Does bevacizumab impact anti-EGFR therapy efficacy in metastatic colorectal cancer?

Anti-EGFR therapy and antiangiogenic therapies are used alone or in combination with chemotherapies to improve survival in metastatic colorectal cancer. However, it is unknown whether pretreatment with antiangiogenic therapy could impact on the efficacy of anti-EGFR therapy. We selected one hundred...

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Autores principales: Derangère, Valentin, Fumet, Jean David, Boidot, Romain, Bengrine, Leila, Limagne, Emeric, Chevriaux, Angélique, Vincent, Julie, Ladoire, Sylvain, Apetoh, Lionel, Rébé, Cédric, Ghiringhelli, François
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4891042/
https://www.ncbi.nlm.nih.gov/pubmed/26824184
http://dx.doi.org/10.18632/oncotarget.7008
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author Derangère, Valentin
Fumet, Jean David
Boidot, Romain
Bengrine, Leila
Limagne, Emeric
Chevriaux, Angélique
Vincent, Julie
Ladoire, Sylvain
Apetoh, Lionel
Rébé, Cédric
Ghiringhelli, François
author_facet Derangère, Valentin
Fumet, Jean David
Boidot, Romain
Bengrine, Leila
Limagne, Emeric
Chevriaux, Angélique
Vincent, Julie
Ladoire, Sylvain
Apetoh, Lionel
Rébé, Cédric
Ghiringhelli, François
author_sort Derangère, Valentin
collection PubMed
description Anti-EGFR therapy and antiangiogenic therapies are used alone or in combination with chemotherapies to improve survival in metastatic colorectal cancer. However, it is unknown whether pretreatment with antiangiogenic therapy could impact on the efficacy of anti-EGFR therapy. We selected one hundred and twenty eight patients diagnosed with advanced colorectal cancer with a KRAS and NRAS unmutated tumor. These patients were treated with cetuximab or panitumumab alone or with chemotherapy as second or third-line. Univariate and multivariate Cox model analysis were performed to estimate the effect of a previous bevacizumab regimen on progression free survival and on overall survival during anti-EGFR therapy. In vitro studies using wild type KRAS and NRAS colon cancer cells were performed to evaluate the impact of VEGF-A on cetuximab-induced cell death. The median progression free survival (PFS) during anti-EGFR treatment was significantly different between the bevacizumab group and the non-bevacizumab group (2.8 and 4 months respectively; p = 0.003). The median overall survival from the beginning of the metastatic disease was similar in the two groups (41.3 and 42 months respectively; p = 0.7). In vitro, VEGF-A induced a resistance toward cetuximab cytotoxicity on three KRAS and NRAS wild type colon cancer cell lines in a VEGFR2 and Stat-3-dependent manner. All in all, our clinical data, supported by in vitro procedures, suggest that a previous anti-VEGF therapy decreases anti-EGFR efficacy. Although these results are observed in a limited cohort, they could be taken into consideration for a better strategy of care for patient suffering from metastatic colorectal cancer.
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spelling pubmed-48910422016-06-20 Does bevacizumab impact anti-EGFR therapy efficacy in metastatic colorectal cancer? Derangère, Valentin Fumet, Jean David Boidot, Romain Bengrine, Leila Limagne, Emeric Chevriaux, Angélique Vincent, Julie Ladoire, Sylvain Apetoh, Lionel Rébé, Cédric Ghiringhelli, François Oncotarget Research Paper Anti-EGFR therapy and antiangiogenic therapies are used alone or in combination with chemotherapies to improve survival in metastatic colorectal cancer. However, it is unknown whether pretreatment with antiangiogenic therapy could impact on the efficacy of anti-EGFR therapy. We selected one hundred and twenty eight patients diagnosed with advanced colorectal cancer with a KRAS and NRAS unmutated tumor. These patients were treated with cetuximab or panitumumab alone or with chemotherapy as second or third-line. Univariate and multivariate Cox model analysis were performed to estimate the effect of a previous bevacizumab regimen on progression free survival and on overall survival during anti-EGFR therapy. In vitro studies using wild type KRAS and NRAS colon cancer cells were performed to evaluate the impact of VEGF-A on cetuximab-induced cell death. The median progression free survival (PFS) during anti-EGFR treatment was significantly different between the bevacizumab group and the non-bevacizumab group (2.8 and 4 months respectively; p = 0.003). The median overall survival from the beginning of the metastatic disease was similar in the two groups (41.3 and 42 months respectively; p = 0.7). In vitro, VEGF-A induced a resistance toward cetuximab cytotoxicity on three KRAS and NRAS wild type colon cancer cell lines in a VEGFR2 and Stat-3-dependent manner. All in all, our clinical data, supported by in vitro procedures, suggest that a previous anti-VEGF therapy decreases anti-EGFR efficacy. Although these results are observed in a limited cohort, they could be taken into consideration for a better strategy of care for patient suffering from metastatic colorectal cancer. Impact Journals LLC 2016-01-25 /pmc/articles/PMC4891042/ /pubmed/26824184 http://dx.doi.org/10.18632/oncotarget.7008 Text en Copyright: © 2016 Derangère et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Derangère, Valentin
Fumet, Jean David
Boidot, Romain
Bengrine, Leila
Limagne, Emeric
Chevriaux, Angélique
Vincent, Julie
Ladoire, Sylvain
Apetoh, Lionel
Rébé, Cédric
Ghiringhelli, François
Does bevacizumab impact anti-EGFR therapy efficacy in metastatic colorectal cancer?
title Does bevacizumab impact anti-EGFR therapy efficacy in metastatic colorectal cancer?
title_full Does bevacizumab impact anti-EGFR therapy efficacy in metastatic colorectal cancer?
title_fullStr Does bevacizumab impact anti-EGFR therapy efficacy in metastatic colorectal cancer?
title_full_unstemmed Does bevacizumab impact anti-EGFR therapy efficacy in metastatic colorectal cancer?
title_short Does bevacizumab impact anti-EGFR therapy efficacy in metastatic colorectal cancer?
title_sort does bevacizumab impact anti-egfr therapy efficacy in metastatic colorectal cancer?
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4891042/
https://www.ncbi.nlm.nih.gov/pubmed/26824184
http://dx.doi.org/10.18632/oncotarget.7008
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