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Risk of antiangiogenic adverse events in metastatic colorectal cancer patients receiving aflibercept in combination with chemotherapy: A meta-analysis
BACKGROUND: Aflibercept has been approved for the treatment of metastatic colorectal cancer for more than a decade, but its antiangiogenesis adverse effect profile during treatment remains unclear. This study is conducted to systematically review the risk of antiangiogenic adverse events in patients...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Lippincott Williams & Wilkins
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10476758/ https://www.ncbi.nlm.nih.gov/pubmed/37657052 http://dx.doi.org/10.1097/MD.0000000000034793 |
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author | Ge, Pu Han, Chunyan Reyila, Abudurousuli Liu, Diyue Hong, Wenying Liu, Jiaxin Zhang, Jinzi Han, Xiao Li, Xialei Huang, Mengjie Fan, Siyuan Kaierdebieke, Ayidana Wu, Xiaoyu Huang, Xiaolu Guo, Weirui Liu, Siyu Bian, Ying |
author_facet | Ge, Pu Han, Chunyan Reyila, Abudurousuli Liu, Diyue Hong, Wenying Liu, Jiaxin Zhang, Jinzi Han, Xiao Li, Xialei Huang, Mengjie Fan, Siyuan Kaierdebieke, Ayidana Wu, Xiaoyu Huang, Xiaolu Guo, Weirui Liu, Siyu Bian, Ying |
author_sort | Ge, Pu |
collection | PubMed |
description | BACKGROUND: Aflibercept has been approved for the treatment of metastatic colorectal cancer for more than a decade, but its antiangiogenesis adverse effect profile during treatment remains unclear. This study is conducted to systematically review the risk of antiangiogenic adverse events in patients with metastatic colorectal cancer receiving aflibercept plus chemotherapy. METHODS: We searched databases, including PubMed, Embase and the Cochrane Library up to September 9, 2021. Relevant randomized controlled trials (RCTs) and single-arm studies were included in the review. Statistical analyses were performed using R to calculate the summary incidence rate of antiangiogenic-related adverse events, odds ratios and 95% CIs. Heterogeneity among the included studies was assessed by subgroup analysis. Publication bias analysis and sensitivity analysis were performed to confirm the reliability of the results. RESULTS: A total of 2889 patients from 10 studies met the inclusion criteria. The quality of the included studies was evaluated as qualified for further quantitative synthesis. In part of single-arm studies, the occurrence rates were 44.2% (95%CI, 39.7–48.7%) for hypertension, 31.3% (95% CI, 19.3–43.3%) for proteinuria, 27.3% (95%CI, 21.2–33.4%) for epistaxis, 22.5% (95%CI, 7.8–37.3%) for hemorrhage events, 8.0% (95%CI, 2.0–14 .0%) for venous thromboembolic event in all grades and 22.6% (95%CI, 19.1–26.2%) for grade III/IV hypertension, 7.4% (95%CI, 6.2–8.5%) for grade III/IV proteinuria. In part of RCT, compared to its counterpart, aflibercept containing arm was associated with the increased incidence rate in hypertension (OR:6.30, 95%CI: 3.49–11.36), proteinuria (OR:4.12, 95%CI: 1.25–13.61), epistaxis (OR:3.71, 95%CI: 2.84–4.85), III/IV hypertension (OR:7.20, 95%CI: 5.23–9.92), III/IV proteinuria (OR:5.13, 95%CI: 3.13–8.41). The funnel plot, Begg test and Egger test were carried out on the primary endpoints, III/IV hypertension rate and III/IV proteinuria rate, the result of which detected no obvious publication bias. No significant difference was observed in subgroup analysis in the primary endpoint between the subgroups stratified by treatment line (firstline or non-firstline), chemotherapy regime (FOLFIRI or others) and study design (RCTs or single-arm trials). CONCLUSION: The available evidence suggests that using aflibercept is associated with an increased risk of antiangiogenic adverse events compared with controls. Further studies are needed to investigate this association. In the appropriate clinical scenario, the use of aflibercept in its approved indications remains justified. However, the results of this study should be interpreted with caution, as some of the evidence comes from single-arm clinical trials. |
format | Online Article Text |
id | pubmed-10476758 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Lippincott Williams & Wilkins |
record_format | MEDLINE/PubMed |
spelling | pubmed-104767582023-09-05 Risk of antiangiogenic adverse events in metastatic colorectal cancer patients receiving aflibercept in combination with chemotherapy: A meta-analysis Ge, Pu Han, Chunyan Reyila, Abudurousuli Liu, Diyue Hong, Wenying Liu, Jiaxin Zhang, Jinzi Han, Xiao Li, Xialei Huang, Mengjie Fan, Siyuan Kaierdebieke, Ayidana Wu, Xiaoyu Huang, Xiaolu Guo, Weirui Liu, Siyu Bian, Ying Medicine (Baltimore) 5700 BACKGROUND: Aflibercept has been approved for the treatment of metastatic colorectal cancer for more than a decade, but its antiangiogenesis adverse effect profile during treatment remains unclear. This study is conducted to systematically review the risk of antiangiogenic adverse events in patients with metastatic colorectal cancer receiving aflibercept plus chemotherapy. METHODS: We searched databases, including PubMed, Embase and the Cochrane Library up to September 9, 2021. Relevant randomized controlled trials (RCTs) and single-arm studies were included in the review. Statistical analyses were performed using R to calculate the summary incidence rate of antiangiogenic-related adverse events, odds ratios and 95% CIs. Heterogeneity among the included studies was assessed by subgroup analysis. Publication bias analysis and sensitivity analysis were performed to confirm the reliability of the results. RESULTS: A total of 2889 patients from 10 studies met the inclusion criteria. The quality of the included studies was evaluated as qualified for further quantitative synthesis. In part of single-arm studies, the occurrence rates were 44.2% (95%CI, 39.7–48.7%) for hypertension, 31.3% (95% CI, 19.3–43.3%) for proteinuria, 27.3% (95%CI, 21.2–33.4%) for epistaxis, 22.5% (95%CI, 7.8–37.3%) for hemorrhage events, 8.0% (95%CI, 2.0–14 .0%) for venous thromboembolic event in all grades and 22.6% (95%CI, 19.1–26.2%) for grade III/IV hypertension, 7.4% (95%CI, 6.2–8.5%) for grade III/IV proteinuria. In part of RCT, compared to its counterpart, aflibercept containing arm was associated with the increased incidence rate in hypertension (OR:6.30, 95%CI: 3.49–11.36), proteinuria (OR:4.12, 95%CI: 1.25–13.61), epistaxis (OR:3.71, 95%CI: 2.84–4.85), III/IV hypertension (OR:7.20, 95%CI: 5.23–9.92), III/IV proteinuria (OR:5.13, 95%CI: 3.13–8.41). The funnel plot, Begg test and Egger test were carried out on the primary endpoints, III/IV hypertension rate and III/IV proteinuria rate, the result of which detected no obvious publication bias. No significant difference was observed in subgroup analysis in the primary endpoint between the subgroups stratified by treatment line (firstline or non-firstline), chemotherapy regime (FOLFIRI or others) and study design (RCTs or single-arm trials). CONCLUSION: The available evidence suggests that using aflibercept is associated with an increased risk of antiangiogenic adverse events compared with controls. Further studies are needed to investigate this association. In the appropriate clinical scenario, the use of aflibercept in its approved indications remains justified. However, the results of this study should be interpreted with caution, as some of the evidence comes from single-arm clinical trials. Lippincott Williams & Wilkins 2023-09-01 /pmc/articles/PMC10476758/ /pubmed/37657052 http://dx.doi.org/10.1097/MD.0000000000034793 Text en Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY) (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | 5700 Ge, Pu Han, Chunyan Reyila, Abudurousuli Liu, Diyue Hong, Wenying Liu, Jiaxin Zhang, Jinzi Han, Xiao Li, Xialei Huang, Mengjie Fan, Siyuan Kaierdebieke, Ayidana Wu, Xiaoyu Huang, Xiaolu Guo, Weirui Liu, Siyu Bian, Ying Risk of antiangiogenic adverse events in metastatic colorectal cancer patients receiving aflibercept in combination with chemotherapy: A meta-analysis |
title | Risk of antiangiogenic adverse events in metastatic colorectal cancer patients receiving aflibercept in combination with chemotherapy: A meta-analysis |
title_full | Risk of antiangiogenic adverse events in metastatic colorectal cancer patients receiving aflibercept in combination with chemotherapy: A meta-analysis |
title_fullStr | Risk of antiangiogenic adverse events in metastatic colorectal cancer patients receiving aflibercept in combination with chemotherapy: A meta-analysis |
title_full_unstemmed | Risk of antiangiogenic adverse events in metastatic colorectal cancer patients receiving aflibercept in combination with chemotherapy: A meta-analysis |
title_short | Risk of antiangiogenic adverse events in metastatic colorectal cancer patients receiving aflibercept in combination with chemotherapy: A meta-analysis |
title_sort | risk of antiangiogenic adverse events in metastatic colorectal cancer patients receiving aflibercept in combination with chemotherapy: a meta-analysis |
topic | 5700 |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10476758/ https://www.ncbi.nlm.nih.gov/pubmed/37657052 http://dx.doi.org/10.1097/MD.0000000000034793 |
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