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First-line treatments in EGFR-mutated advanced non-small cell lung cancer: A network meta-analysis

BACKGROUND: It remains unknown which is the optimal first-line treatment regimen for patients with advanced epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). We performed a network meta-analysis to address this important issue. METHODS: PubMed, Embase, Cochrane Libr...

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Autores principales: Zhang, Hongwei, Chen, Jun, Liu, Tingting, Dang, Jun, Li, Guang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6776360/
https://www.ncbi.nlm.nih.gov/pubmed/31581247
http://dx.doi.org/10.1371/journal.pone.0223530
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author Zhang, Hongwei
Chen, Jun
Liu, Tingting
Dang, Jun
Li, Guang
author_facet Zhang, Hongwei
Chen, Jun
Liu, Tingting
Dang, Jun
Li, Guang
author_sort Zhang, Hongwei
collection PubMed
description BACKGROUND: It remains unknown which is the optimal first-line treatment regimen for patients with advanced epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). We performed a network meta-analysis to address this important issue. METHODS: PubMed, Embase, Cochrane Library, Web of Science and major international scientific meetings were searched for relevant randomized controlled trials (RCTs). Progression-free survival (PFS) data was the primary outcome of interest, and overall survival (OS) and serious adverse events (SAEs) were the secondary outcomes of interests, reported as hazard ratio (HR) or odds ratio (OR) and 95% confidence intervals (CIs). RESULTS: 25 RCTs with a total of 5005 patients randomized to receive seven treatments were included in the meta-analysis. Third-generation tyrosine kinase inhibitor (TKI) (osimertinib) and first-generation TKIs (F-TKIs) in combination with chemotherapy (F-TKIs+CT) were more effective than F-TKIs alone in terms of PFS (HR = 0.46, 95% CI: 0.22–0.93; P = 0.031 and HR = 0.62, 95% CI: 0.39–0.98; P = 0.041) and OS (HR = 0.63, 95% CI: 0.43–0.91; P = 0.014 and HR = 0.73, 95% CI: 0.57–0.92; P = 0.008). Second-generation TKIs (S-TKIs) showed significant OS advantage over F-TKIs (HR = 0.83, 95% CI: 0.70–0.99; P = 0.04). Based on treatment ranking in terms of PFS and OS, osimertinib had the highest probability of being the most effective treatment (89% and 86%) and with the best tolerability. F-TKIs+CT was ranked the second-most effective regimen, but with relatively high risk of SAEs. CONCLUSIONS: Osimertinib seemed to be the most preferable first-line treatment in advanced EGFR-mutated NSCLC. However, limitations of the study including a single RCT investigating osimertinib and immature OS data need to be considered.
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spelling pubmed-67763602019-10-11 First-line treatments in EGFR-mutated advanced non-small cell lung cancer: A network meta-analysis Zhang, Hongwei Chen, Jun Liu, Tingting Dang, Jun Li, Guang PLoS One Research Article BACKGROUND: It remains unknown which is the optimal first-line treatment regimen for patients with advanced epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). We performed a network meta-analysis to address this important issue. METHODS: PubMed, Embase, Cochrane Library, Web of Science and major international scientific meetings were searched for relevant randomized controlled trials (RCTs). Progression-free survival (PFS) data was the primary outcome of interest, and overall survival (OS) and serious adverse events (SAEs) were the secondary outcomes of interests, reported as hazard ratio (HR) or odds ratio (OR) and 95% confidence intervals (CIs). RESULTS: 25 RCTs with a total of 5005 patients randomized to receive seven treatments were included in the meta-analysis. Third-generation tyrosine kinase inhibitor (TKI) (osimertinib) and first-generation TKIs (F-TKIs) in combination with chemotherapy (F-TKIs+CT) were more effective than F-TKIs alone in terms of PFS (HR = 0.46, 95% CI: 0.22–0.93; P = 0.031 and HR = 0.62, 95% CI: 0.39–0.98; P = 0.041) and OS (HR = 0.63, 95% CI: 0.43–0.91; P = 0.014 and HR = 0.73, 95% CI: 0.57–0.92; P = 0.008). Second-generation TKIs (S-TKIs) showed significant OS advantage over F-TKIs (HR = 0.83, 95% CI: 0.70–0.99; P = 0.04). Based on treatment ranking in terms of PFS and OS, osimertinib had the highest probability of being the most effective treatment (89% and 86%) and with the best tolerability. F-TKIs+CT was ranked the second-most effective regimen, but with relatively high risk of SAEs. CONCLUSIONS: Osimertinib seemed to be the most preferable first-line treatment in advanced EGFR-mutated NSCLC. However, limitations of the study including a single RCT investigating osimertinib and immature OS data need to be considered. Public Library of Science 2019-10-03 /pmc/articles/PMC6776360/ /pubmed/31581247 http://dx.doi.org/10.1371/journal.pone.0223530 Text en © 2019 Zhang et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Zhang, Hongwei
Chen, Jun
Liu, Tingting
Dang, Jun
Li, Guang
First-line treatments in EGFR-mutated advanced non-small cell lung cancer: A network meta-analysis
title First-line treatments in EGFR-mutated advanced non-small cell lung cancer: A network meta-analysis
title_full First-line treatments in EGFR-mutated advanced non-small cell lung cancer: A network meta-analysis
title_fullStr First-line treatments in EGFR-mutated advanced non-small cell lung cancer: A network meta-analysis
title_full_unstemmed First-line treatments in EGFR-mutated advanced non-small cell lung cancer: A network meta-analysis
title_short First-line treatments in EGFR-mutated advanced non-small cell lung cancer: A network meta-analysis
title_sort first-line treatments in egfr-mutated advanced non-small cell lung cancer: a network meta-analysis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6776360/
https://www.ncbi.nlm.nih.gov/pubmed/31581247
http://dx.doi.org/10.1371/journal.pone.0223530
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