Safety Assessment on Serious Adverse Events of Targeted Therapeutic Agents Prescribed for RAS Wild-Type Metastatic Colorectal Cancer: Systematic Review and Network Meta-Analysis
Despite substantially elevated risk of serious adverse events (SAEs) from targeted therapy in combination with chemotherapy, comprehensive pharmacovigilance research is limited. This study aims to systematically assess SAE risks of commonly prescribed targeted agents (bevacizumab, cetuximab, and pan...
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| Veröffentlicht in: | International journal of environmental research and public health 2022-07, Vol.19 (15), p.9196 |
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| creator | Choi, Yeo Jin Choi, Chang-Young Rhie, Sandy Jeong Shin, Sooyoung |
| description | Despite substantially elevated risk of serious adverse events (SAEs) from targeted therapy in combination with chemotherapy, comprehensive pharmacovigilance research is limited. This study aims to systematically assess SAE risks of commonly prescribed targeted agents (bevacizumab, cetuximab, and panitumumab) in patients with rat sarcoma viral oncogene homolog (RAS) wild-type metastatic colon cancer. Keyword searches of Cochrane Library, Clinical Key and MEDLINE were conducted per PRISMA-NMA guidelines. Frequentist network meta-analysis was performed with eight randomized controlled trials to compare relative risk (RR) of 21 SAE profiles. The risks of hematological, gastrointestinal, neurological SAE were insignificant among targeted agents (p > 0.05). The risk of serious hypertension was substantially elevated in bevacizumab-based chemotherapy (p < 0.05), whereas panitumumab-based chemotherapy had markedly elevated risk of serious thromboembolism (RR 3.65; 95% CI 1.30−10.26). Although both cetuximab and panitumumab demonstrated increased risk of serious dermatological and renal toxicities, panitumumab-based chemotherapy has relatively higher risk of skin toxicity (RR 15.22; 95% CI 7.17−32.35), mucositis (RR 3.18; 95% CI 1.52−6.65), hypomagnesemia (RR 20.10; 95% CI 5.92−68.21), and dehydration (RR 2.81; 95% CI 1.03−7.67) than cetuximab-based chemotherapy. Thus, further studies on risk stratification and SAE management are warranted for safe administration of targeted agents. |
| doi_str_mv | 10.3390/ijerph19159196 |
| format | Article |
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This study aims to systematically assess SAE risks of commonly prescribed targeted agents (bevacizumab, cetuximab, and panitumumab) in patients with rat sarcoma viral oncogene homolog (RAS) wild-type metastatic colon cancer. Keyword searches of Cochrane Library, Clinical Key and MEDLINE were conducted per PRISMA-NMA guidelines. Frequentist network meta-analysis was performed with eight randomized controlled trials to compare relative risk (RR) of 21 SAE profiles. The risks of hematological, gastrointestinal, neurological SAE were insignificant among targeted agents (p > 0.05). The risk of serious hypertension was substantially elevated in bevacizumab-based chemotherapy (p < 0.05), whereas panitumumab-based chemotherapy had markedly elevated risk of serious thromboembolism (RR 3.65; 95% CI 1.30−10.26). Although both cetuximab and panitumumab demonstrated increased risk of serious dermatological and renal toxicities, panitumumab-based chemotherapy has relatively higher risk of skin toxicity (RR 15.22; 95% CI 7.17−32.35), mucositis (RR 3.18; 95% CI 1.52−6.65), hypomagnesemia (RR 20.10; 95% CI 5.92−68.21), and dehydration (RR 2.81; 95% CI 1.03−7.67) than cetuximab-based chemotherapy. Thus, further studies on risk stratification and SAE management are warranted for safe administration of targeted agents.</description><identifier>ISSN: 1660-4601</identifier><identifier>ISSN: 1661-7827</identifier><identifier>EISSN: 1660-4601</identifier><identifier>DOI: 10.3390/ijerph19159196</identifier><identifier>PMID: 35954563</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Adverse events ; Antibodies ; Antineoplastic Agents - adverse effects ; Bevacizumab ; Bevacizumab - adverse effects ; Bias ; Cancer therapies ; Cetuximab - adverse effects ; Chemical compounds ; Chemotherapy ; Clinical outcomes ; Clinical trials ; Colon ; Colon cancer ; Colorectal cancer ; Colorectal carcinoma ; Colorectal Neoplasms - drug therapy ; Colorectal Neoplasms - pathology ; Dehydration ; Homology ; Humans ; Hypertension ; Hypomagnesemia ; Intervention ; Medical prognosis ; Meta-analysis ; Metastases ; Metastasis ; Monoclonal antibodies ; Mucositis ; Network Meta-Analysis ; Panitumumab - adverse effects ; Patients ; Pharmacology ; Pharmacovigilance ; Risk management ; Sarcoma ; Systematic review ; Targeted cancer therapy ; Thromboembolism ; Toxicity ; Vascular endothelial growth factor</subject><ispartof>International journal of environmental research and public health, 2022-07, Vol.19 (15), p.9196</ispartof><rights>2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). 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This study aims to systematically assess SAE risks of commonly prescribed targeted agents (bevacizumab, cetuximab, and panitumumab) in patients with rat sarcoma viral oncogene homolog (RAS) wild-type metastatic colon cancer. Keyword searches of Cochrane Library, Clinical Key and MEDLINE were conducted per PRISMA-NMA guidelines. Frequentist network meta-analysis was performed with eight randomized controlled trials to compare relative risk (RR) of 21 SAE profiles. The risks of hematological, gastrointestinal, neurological SAE were insignificant among targeted agents (p > 0.05). The risk of serious hypertension was substantially elevated in bevacizumab-based chemotherapy (p < 0.05), whereas panitumumab-based chemotherapy had markedly elevated risk of serious thromboembolism (RR 3.65; 95% CI 1.30−10.26). Although both cetuximab and panitumumab demonstrated increased risk of serious dermatological and renal toxicities, panitumumab-based chemotherapy has relatively higher risk of skin toxicity (RR 15.22; 95% CI 7.17−32.35), mucositis (RR 3.18; 95% CI 1.52−6.65), hypomagnesemia (RR 20.10; 95% CI 5.92−68.21), and dehydration (RR 2.81; 95% CI 1.03−7.67) than cetuximab-based chemotherapy. Thus, further studies on risk stratification and SAE management are warranted for safe administration of targeted agents.</description><subject>Adverse events</subject><subject>Antibodies</subject><subject>Antineoplastic Agents - adverse effects</subject><subject>Bevacizumab</subject><subject>Bevacizumab - adverse effects</subject><subject>Bias</subject><subject>Cancer therapies</subject><subject>Cetuximab - adverse effects</subject><subject>Chemical compounds</subject><subject>Chemotherapy</subject><subject>Clinical outcomes</subject><subject>Clinical trials</subject><subject>Colon</subject><subject>Colon cancer</subject><subject>Colorectal cancer</subject><subject>Colorectal carcinoma</subject><subject>Colorectal Neoplasms - drug therapy</subject><subject>Colorectal Neoplasms - pathology</subject><subject>Dehydration</subject><subject>Homology</subject><subject>Humans</subject><subject>Hypertension</subject><subject>Hypomagnesemia</subject><subject>Intervention</subject><subject>Medical prognosis</subject><subject>Meta-analysis</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Monoclonal antibodies</subject><subject>Mucositis</subject><subject>Network Meta-Analysis</subject><subject>Panitumumab - adverse effects</subject><subject>Patients</subject><subject>Pharmacology</subject><subject>Pharmacovigilance</subject><subject>Risk management</subject><subject>Sarcoma</subject><subject>Systematic review</subject><subject>Targeted cancer therapy</subject><subject>Thromboembolism</subject><subject>Toxicity</subject><subject>Vascular endothelial growth factor</subject><issn>1660-4601</issn><issn>1661-7827</issn><issn>1660-4601</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><recordid>eNpVkUFv1DAQhS1ERUvhyhFZ4pzWjh1vzAEpWhWoVArqRuIYOc5k10s2Tj3OVvlZ_EPSbana04z0vXkzo0fIB87OhNDs3G0hDBuueaa5Vq_ICVeKJVIx_vpZf0zeIm4ZE7lU-g05FpnOZKbECfm7Mi3EiRaIgLiDPlLf0xUE50ekRbOHgEAv9jNA6ltamrCGCA0tNxDMAGN0lhbrA_4VAG1w9UxbH-hNsaK_Xdck5TQA_QHRYDT38qXvfAAbTUeXprcQPtPVhBF2B3oDewd31PQNvYZ458Ofw2xS9Kab0OE7ctSaDuH9Yz0l5deLcvk9ufr57XJZXCVW8jwmFqRaSNY0zGpb2zqXbW1YDamsQXPODfBGg80XshE5k0ZlLONMaV6nbatTcUq-PNgOY72Dxs4fBtNVQ3A7E6bKG1e9JL3bVGu_r7RQeSrZbPDp0SD42xEwVls_hvkJrNIFY0porfJZdfagssEjBmifNnBW3SdcvUx4Hvj4_K4n-f9IxT8OXqeb</recordid><startdate>20220727</startdate><enddate>20220727</enddate><creator>Choi, Yeo Jin</creator><creator>Choi, Chang-Young</creator><creator>Rhie, Sandy Jeong</creator><creator>Shin, Sooyoung</creator><general>MDPI AG</general><general>MDPI</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-2388-1122</orcidid><orcidid>https://orcid.org/0000-0002-0635-4374</orcidid><orcidid>https://orcid.org/0000-0003-2554-3370</orcidid></search><sort><creationdate>20220727</creationdate><title>Safety Assessment on Serious Adverse Events of Targeted Therapeutic Agents Prescribed for RAS Wild-Type Metastatic Colorectal Cancer: Systematic Review and Network Meta-Analysis</title><author>Choi, Yeo Jin ; 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This study aims to systematically assess SAE risks of commonly prescribed targeted agents (bevacizumab, cetuximab, and panitumumab) in patients with rat sarcoma viral oncogene homolog (RAS) wild-type metastatic colon cancer. Keyword searches of Cochrane Library, Clinical Key and MEDLINE were conducted per PRISMA-NMA guidelines. Frequentist network meta-analysis was performed with eight randomized controlled trials to compare relative risk (RR) of 21 SAE profiles. The risks of hematological, gastrointestinal, neurological SAE were insignificant among targeted agents (p > 0.05). The risk of serious hypertension was substantially elevated in bevacizumab-based chemotherapy (p < 0.05), whereas panitumumab-based chemotherapy had markedly elevated risk of serious thromboembolism (RR 3.65; 95% CI 1.30−10.26). Although both cetuximab and panitumumab demonstrated increased risk of serious dermatological and renal toxicities, panitumumab-based chemotherapy has relatively higher risk of skin toxicity (RR 15.22; 95% CI 7.17−32.35), mucositis (RR 3.18; 95% CI 1.52−6.65), hypomagnesemia (RR 20.10; 95% CI 5.92−68.21), and dehydration (RR 2.81; 95% CI 1.03−7.67) than cetuximab-based chemotherapy. Thus, further studies on risk stratification and SAE management are warranted for safe administration of targeted agents.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>35954563</pmid><doi>10.3390/ijerph19159196</doi><orcidid>https://orcid.org/0000-0003-2388-1122</orcidid><orcidid>https://orcid.org/0000-0002-0635-4374</orcidid><orcidid>https://orcid.org/0000-0003-2554-3370</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Adverse events Antibodies Antineoplastic Agents - adverse effects Bevacizumab Bevacizumab - adverse effects Bias Cancer therapies Cetuximab - adverse effects Chemical compounds Chemotherapy Clinical outcomes Clinical trials Colon Colon cancer Colorectal cancer Colorectal carcinoma Colorectal Neoplasms - drug therapy Colorectal Neoplasms - pathology Dehydration Homology Humans Hypertension Hypomagnesemia Intervention Medical prognosis Meta-analysis Metastases Metastasis Monoclonal antibodies Mucositis Network Meta-Analysis Panitumumab - adverse effects Patients Pharmacology Pharmacovigilance Risk management Sarcoma Systematic review Targeted cancer therapy Thromboembolism Toxicity Vascular endothelial growth factor |
| title | Safety Assessment on Serious Adverse Events of Targeted Therapeutic Agents Prescribed for RAS Wild-Type Metastatic Colorectal Cancer: Systematic Review and Network Meta-Analysis |
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