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

<h4>Background</h4>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.<h4>Methods<...

Full description

Saved in:
Bibliographic Details
Main Authors: Hongwei Zhang, Jun Chen, Tingting Liu, Jun Dang, Guang Li
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2019-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0223530&type=printable
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850076284079570944
author Hongwei Zhang
Jun Chen
Tingting Liu
Jun Dang
Guang Li
author_facet Hongwei Zhang
Jun Chen
Tingting Liu
Jun Dang
Guang Li
author_sort Hongwei Zhang
collection DOAJ
description <h4>Background</h4>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.<h4>Methods</h4>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).<h4>Results</h4>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.<h4>Conclusions</h4>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.
format Article
id doaj-art-4b1531c4d963413eb91fa19d47d2a86d
institution DOAJ
issn 1932-6203
language English
publishDate 2019-01-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS ONE
spelling doaj-art-4b1531c4d963413eb91fa19d47d2a86d2025-08-20T02:46:04ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-011410e022353010.1371/journal.pone.0223530First-line treatments in EGFR-mutated advanced non-small cell lung cancer: A network meta-analysis.Hongwei ZhangJun ChenTingting LiuJun DangGuang Li<h4>Background</h4>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.<h4>Methods</h4>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).<h4>Results</h4>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.<h4>Conclusions</h4>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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0223530&type=printable
spellingShingle Hongwei Zhang
Jun Chen
Tingting Liu
Jun Dang
Guang Li
First-line treatments in EGFR-mutated advanced non-small cell lung cancer: A network meta-analysis.
PLoS ONE
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
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0223530&type=printable
work_keys_str_mv AT hongweizhang firstlinetreatmentsinegfrmutatedadvancednonsmallcelllungcanceranetworkmetaanalysis
AT junchen firstlinetreatmentsinegfrmutatedadvancednonsmallcelllungcanceranetworkmetaanalysis
AT tingtingliu firstlinetreatmentsinegfrmutatedadvancednonsmallcelllungcanceranetworkmetaanalysis
AT jundang firstlinetreatmentsinegfrmutatedadvancednonsmallcelllungcanceranetworkmetaanalysis
AT guangli firstlinetreatmentsinegfrmutatedadvancednonsmallcelllungcanceranetworkmetaanalysis