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Efficacy of Next-Generation EGFR-TKIs in Patients With Non-Small Cell Lung Cancer: A Meta-Analysis of Randomized Controlled Trials

Background: The efficacy of next-generation epidermal growth factor receptor-tyrosine kinase inhibitors in patients with advanced non-small cell lung cancer who have failed first-generation epidermal growth factor receptor-tyrosine kinase inhibitors still remains under investigation. Objective: The...

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Published in:Technology in cancer research & treatment 2020, Vol.19, p.1533033820940426-1533033820940426
Main Authors: Qi, Yi-Tian, Hou, Yi, Qi, Liang-Chen
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description Background: The efficacy of next-generation epidermal growth factor receptor-tyrosine kinase inhibitors in patients with advanced non-small cell lung cancer who have failed first-generation epidermal growth factor receptor-tyrosine kinase inhibitors still remains under investigation. Objective: The aim of this meta-analysis was to systematically assess the efficacy and safety profiles of next-generation epidermal growth factor receptor-tyrosine kinase inhibitors in patients with advanced non-small cell lung cancer who failed first-generation epidermal growth factor receptor-tyrosine kinase inhibitors. Methods: We performed a comprehensive search of several electronic databases up to September 2018 to identify clinical trials. The primary end point was overall survival, progression-free survival, disease controlled rate, objective response rate, and adverse events. Epidermal growth factor receptor-tyrosine kinase inhibitor emergent severe adverse events (grade ≥ 3) were analyzed. Odds ratio along with 95% confidence interval were utilized for main outcome analysis. Results: In total, we had 3 randomized controlled trials in this analysis. The group of next-generation epidermal growth factor receptor-tyrosine kinase inhibitors had significantly improved progression-free survival (odds ratio = 0.34, 95% confidence interval = 0.29-0.40, P < .00001), as well as objective response rate (odds ratio = 10.48, 95% confidence interval = 3.87-28.34, P < .00001) and disease controlled rate (odds ratio = 6.03, 95% confidence interval = 4.41-8.25, P < .00001). However, there was no significant difference in overall survival with next-generation epidermal growth factor receptor-tyrosine kinase inhibitors (odds ratio = 1.05, 95% confidence interval = 0.85-1.31, P = .66). Meanwhile, the odds ratio for treatment-emergent severe adverse events (diarrhea, rash/acne, nausea, vomiting, anemia) between patients who received next-generation epidermal growth factor receptor-tyrosine kinase inhibitors and those who received first-generation epidermal growth factor receptor-tyrosine kinase inhibitors did not show safety benefit (P > .05). Conclusions: Next-generation epidermal growth factor receptor-tyrosine kinase inhibitors were shown to be the better agent to achieve higher response rate and longer progression-free survival in patients with non-small cell lung cancer as the later-line therapy for previously treated patients with first-generation epidermal growth factor receptor-ty
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Objective: The aim of this meta-analysis was to systematically assess the efficacy and safety profiles of next-generation epidermal growth factor receptor-tyrosine kinase inhibitors in patients with advanced non-small cell lung cancer who failed first-generation epidermal growth factor receptor-tyrosine kinase inhibitors. Methods: We performed a comprehensive search of several electronic databases up to September 2018 to identify clinical trials. The primary end point was overall survival, progression-free survival, disease controlled rate, objective response rate, and adverse events. Epidermal growth factor receptor-tyrosine kinase inhibitor emergent severe adverse events (grade ≥ 3) were analyzed. Odds ratio along with 95% confidence interval were utilized for main outcome analysis. Results: In total, we had 3 randomized controlled trials in this analysis. The group of next-generation epidermal growth factor receptor-tyrosine kinase inhibitors had significantly improved progression-free survival (odds ratio = 0.34, 95% confidence interval = 0.29-0.40, P &lt; .00001), as well as objective response rate (odds ratio = 10.48, 95% confidence interval = 3.87-28.34, P &lt; .00001) and disease controlled rate (odds ratio = 6.03, 95% confidence interval = 4.41-8.25, P &lt; .00001). However, there was no significant difference in overall survival with next-generation epidermal growth factor receptor-tyrosine kinase inhibitors (odds ratio = 1.05, 95% confidence interval = 0.85-1.31, P = .66). Meanwhile, the odds ratio for treatment-emergent severe adverse events (diarrhea, rash/acne, nausea, vomiting, anemia) between patients who received next-generation epidermal growth factor receptor-tyrosine kinase inhibitors and those who received first-generation epidermal growth factor receptor-tyrosine kinase inhibitors did not show safety benefit (P &gt; .05). Conclusions: Next-generation epidermal growth factor receptor-tyrosine kinase inhibitors were shown to be the better agent to achieve higher response rate and longer progression-free survival in patients with non-small cell lung cancer as the later-line therapy for previously treated patients with first-generation epidermal growth factor receptor-tyrosine kinase inhibitors. Meanwhile, they did not achieve benefit in overall survival and safety compared with the chemotherapy group. Further research is needed to develop a database of all EGFR mutations and their individual impacts on the various treatments.</description><identifier>ISSN: 1533-0346</identifier><identifier>EISSN: 1533-0338</identifier><identifier>DOI: 10.1177/1533033820940426</identifier><identifier>PMID: 32723164</identifier><language>eng</language><publisher>Los Angeles, CA: SAGE Publications</publisher><subject>Acne ; Adverse events ; Cancer therapies ; Chemotherapy ; Clinical trials ; Confidence intervals ; Diarrhea ; Enzyme inhibitors ; Epidermal growth factor ; Epidermal growth factor receptors ; Lung cancer ; Meta-analysis ; Nausea ; Non-small cell lung carcinoma ; Original ; Patients ; Protein-tyrosine kinase ; Response rates ; Safety ; Small cell lung carcinoma ; Vomiting</subject><ispartof>Technology in cancer research &amp; treatment, 2020, Vol.19, p.1533033820940426-1533033820940426</ispartof><rights>The Author(s) 2020</rights><rights>The Author(s) 2020. This work is licensed under the Creative Commons Attribution – Non-Commercial License https://creativecommons.org/licenses/by-nc/4.0/ (the “License”). 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Objective: The aim of this meta-analysis was to systematically assess the efficacy and safety profiles of next-generation epidermal growth factor receptor-tyrosine kinase inhibitors in patients with advanced non-small cell lung cancer who failed first-generation epidermal growth factor receptor-tyrosine kinase inhibitors. Methods: We performed a comprehensive search of several electronic databases up to September 2018 to identify clinical trials. The primary end point was overall survival, progression-free survival, disease controlled rate, objective response rate, and adverse events. Epidermal growth factor receptor-tyrosine kinase inhibitor emergent severe adverse events (grade ≥ 3) were analyzed. Odds ratio along with 95% confidence interval were utilized for main outcome analysis. Results: In total, we had 3 randomized controlled trials in this analysis. The group of next-generation epidermal growth factor receptor-tyrosine kinase inhibitors had significantly improved progression-free survival (odds ratio = 0.34, 95% confidence interval = 0.29-0.40, P &lt; .00001), as well as objective response rate (odds ratio = 10.48, 95% confidence interval = 3.87-28.34, P &lt; .00001) and disease controlled rate (odds ratio = 6.03, 95% confidence interval = 4.41-8.25, P &lt; .00001). However, there was no significant difference in overall survival with next-generation epidermal growth factor receptor-tyrosine kinase inhibitors (odds ratio = 1.05, 95% confidence interval = 0.85-1.31, P = .66). Meanwhile, the odds ratio for treatment-emergent severe adverse events (diarrhea, rash/acne, nausea, vomiting, anemia) between patients who received next-generation epidermal growth factor receptor-tyrosine kinase inhibitors and those who received first-generation epidermal growth factor receptor-tyrosine kinase inhibitors did not show safety benefit (P &gt; .05). Conclusions: Next-generation epidermal growth factor receptor-tyrosine kinase inhibitors were shown to be the better agent to achieve higher response rate and longer progression-free survival in patients with non-small cell lung cancer as the later-line therapy for previously treated patients with first-generation epidermal growth factor receptor-tyrosine kinase inhibitors. Meanwhile, they did not achieve benefit in overall survival and safety compared with the chemotherapy group. Further research is needed to develop a database of all EGFR mutations and their individual impacts on the various treatments.</description><subject>Acne</subject><subject>Adverse events</subject><subject>Cancer therapies</subject><subject>Chemotherapy</subject><subject>Clinical trials</subject><subject>Confidence intervals</subject><subject>Diarrhea</subject><subject>Enzyme inhibitors</subject><subject>Epidermal growth factor</subject><subject>Epidermal growth factor receptors</subject><subject>Lung cancer</subject><subject>Meta-analysis</subject><subject>Nausea</subject><subject>Non-small cell lung carcinoma</subject><subject>Original</subject><subject>Patients</subject><subject>Protein-tyrosine kinase</subject><subject>Response rates</subject><subject>Safety</subject><subject>Small cell lung carcinoma</subject><subject>Vomiting</subject><issn>1533-0346</issn><issn>1533-0338</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>AFRWT</sourceid><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNp1kk1vEzEQhlcIREvgzglZ4sJlwV_r3eWAFEVpiAgFlSCOq1nvOHW0sYu9QU2P_HIcUgKtxMVjvX7mtT0zWfac0deMleUbVghBhag4rSWVXD3ITvdSvtceHvdSnWRPYlxTypUS7HF2InjJBVPyNPs5NcZq0DviDTnH6yGfocMAg_WOTGdnF_nywzwS68jnpKEbIvlmh0ty7l3-ZQN9TyaYlsXWrcgEnMbwlozJRxwgHzvod9HGvfMFuM5v7A12ZOLdEHzfp-0yWOjj0-yRSQGf3cZR9vVsupy8zxefZvPJeJHrgldDLmtA1bIOaWsMVG2rsTRAhdKsUrygUAnQqEXBuCiFUi2oimNh0KCsjW7FKJsffDsP6-Yq2A2EXePBNr8FH1YNhMHqHhsqaUVZXZeyK2XB64p3AikUgrYauoInr3cHr6ttu8FOp8IE6O-Y3j1x9rJZ-R9NKWomU89G2atbg-C_bzEOzcZGnUoJDv02NlzySrKaKpbQl_fQtd-GVNxEFSXdd7UuE0UPlA4-xoDm-BhGm_2wNPeHJaW8-PcTx4Q_05GA_ABEWOHfW_9r-AuGOsXr</recordid><startdate>2020</startdate><enddate>2020</enddate><creator>Qi, Yi-Tian</creator><creator>Hou, Yi</creator><creator>Qi, Liang-Chen</creator><general>SAGE Publications</general><general>Sage Publications Ltd</general><general>SAGE Publishing</general><scope>AFRWT</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</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>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0001-5111-9229</orcidid></search><sort><creationdate>2020</creationdate><title>Efficacy of Next-Generation EGFR-TKIs in Patients With Non-Small Cell Lung Cancer: A Meta-Analysis of Randomized Controlled Trials</title><author>Qi, Yi-Tian ; Hou, Yi ; Qi, Liang-Chen</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c528t-49ae6b1de0bffa8bbce7fa036c186250a83acec351237366ba682e5fefe49fcb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Acne</topic><topic>Adverse events</topic><topic>Cancer therapies</topic><topic>Chemotherapy</topic><topic>Clinical trials</topic><topic>Confidence intervals</topic><topic>Diarrhea</topic><topic>Enzyme inhibitors</topic><topic>Epidermal growth factor</topic><topic>Epidermal growth factor receptors</topic><topic>Lung cancer</topic><topic>Meta-analysis</topic><topic>Nausea</topic><topic>Non-small cell lung carcinoma</topic><topic>Original</topic><topic>Patients</topic><topic>Protein-tyrosine kinase</topic><topic>Response rates</topic><topic>Safety</topic><topic>Small cell lung carcinoma</topic><topic>Vomiting</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Qi, Yi-Tian</creatorcontrib><creatorcontrib>Hou, Yi</creatorcontrib><creatorcontrib>Qi, Liang-Chen</creatorcontrib><collection>SAGE Open Access</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Health &amp; 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treatment</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Qi, Yi-Tian</au><au>Hou, Yi</au><au>Qi, Liang-Chen</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Efficacy of Next-Generation EGFR-TKIs in Patients With Non-Small Cell Lung Cancer: A Meta-Analysis of Randomized Controlled Trials</atitle><jtitle>Technology in cancer research &amp; treatment</jtitle><addtitle>Technol Cancer Res Treat</addtitle><date>2020</date><risdate>2020</risdate><volume>19</volume><spage>1533033820940426</spage><epage>1533033820940426</epage><pages>1533033820940426-1533033820940426</pages><issn>1533-0346</issn><eissn>1533-0338</eissn><abstract>Background: The efficacy of next-generation epidermal growth factor receptor-tyrosine kinase inhibitors in patients with advanced non-small cell lung cancer who have failed first-generation epidermal growth factor receptor-tyrosine kinase inhibitors still remains under investigation. Objective: The aim of this meta-analysis was to systematically assess the efficacy and safety profiles of next-generation epidermal growth factor receptor-tyrosine kinase inhibitors in patients with advanced non-small cell lung cancer who failed first-generation epidermal growth factor receptor-tyrosine kinase inhibitors. Methods: We performed a comprehensive search of several electronic databases up to September 2018 to identify clinical trials. The primary end point was overall survival, progression-free survival, disease controlled rate, objective response rate, and adverse events. Epidermal growth factor receptor-tyrosine kinase inhibitor emergent severe adverse events (grade ≥ 3) were analyzed. Odds ratio along with 95% confidence interval were utilized for main outcome analysis. Results: In total, we had 3 randomized controlled trials in this analysis. The group of next-generation epidermal growth factor receptor-tyrosine kinase inhibitors had significantly improved progression-free survival (odds ratio = 0.34, 95% confidence interval = 0.29-0.40, P &lt; .00001), as well as objective response rate (odds ratio = 10.48, 95% confidence interval = 3.87-28.34, P &lt; .00001) and disease controlled rate (odds ratio = 6.03, 95% confidence interval = 4.41-8.25, P &lt; .00001). However, there was no significant difference in overall survival with next-generation epidermal growth factor receptor-tyrosine kinase inhibitors (odds ratio = 1.05, 95% confidence interval = 0.85-1.31, P = .66). Meanwhile, the odds ratio for treatment-emergent severe adverse events (diarrhea, rash/acne, nausea, vomiting, anemia) between patients who received next-generation epidermal growth factor receptor-tyrosine kinase inhibitors and those who received first-generation epidermal growth factor receptor-tyrosine kinase inhibitors did not show safety benefit (P &gt; .05). Conclusions: Next-generation epidermal growth factor receptor-tyrosine kinase inhibitors were shown to be the better agent to achieve higher response rate and longer progression-free survival in patients with non-small cell lung cancer as the later-line therapy for previously treated patients with first-generation epidermal growth factor receptor-tyrosine kinase inhibitors. Meanwhile, they did not achieve benefit in overall survival and safety compared with the chemotherapy group. Further research is needed to develop a database of all EGFR mutations and their individual impacts on the various treatments.</abstract><cop>Los Angeles, CA</cop><pub>SAGE Publications</pub><pmid>32723164</pmid><doi>10.1177/1533033820940426</doi><orcidid>https://orcid.org/0000-0001-5111-9229</orcidid><oa>free_for_read</oa></addata></record>
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subjects Acne
Adverse events
Cancer therapies
Chemotherapy
Clinical trials
Confidence intervals
Diarrhea
Enzyme inhibitors
Epidermal growth factor
Epidermal growth factor receptors
Lung cancer
Meta-analysis
Nausea
Non-small cell lung carcinoma
Original
Patients
Protein-tyrosine kinase
Response rates
Safety
Small cell lung carcinoma
Vomiting
title Efficacy of Next-Generation EGFR-TKIs in Patients With Non-Small Cell Lung Cancer: A Meta-Analysis of Randomized Controlled Trials
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