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<...
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Public Library of Science (PLoS)
2019-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0223530&type=printable |
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| 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 |
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