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. 2019 Oct 3;14(10):e0223530.
doi: 10.1371/journal.pone.0223530. eCollection 2019.

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

Hongwei Zhang  1 , Jun Chen  2 , Tingting Liu  3 , Jun Dang  1 , Guang Li  1
Affiliations

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

Hongwei Zhang et al. PLoS One. .

Abstract

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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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Literature search and selection.
Fig 2
Fig 2. Network of eligible comparisons.
The size of the nodes is proportional to the number of patients (in parentheses) randomized to receive the treatment. The width of the lines is proportional to the number of trials (beside the line) comparing the connected treatments. TKIs, tyrosine kinase inhibitor; F, first-generation; S, second-generation; Bev, bevacizumab; CT, chemotherapy; Lin, Linsitinib.
Fig 3
Fig 3. The treatment rankings based on SUCRA.
(a) progression-free survival; (b) overall survival; (c) serious adverse events. SUCRA, surface under the cumulative ranking curves; TKIs, tyrosine kinase inhibitor; F, first-generation; S, second-generation; Bev, bevacizumab; CT, chemotherapy; Lin, Linsitinib.
Fig 4
Fig 4. Ranking plot based simultaneously on efficacy (x-axis: SUCRA value of overall survival) and tolerability (y-axis: 1-SUCRA value of serious adverse events).
SUCRA, surface under the cumulative ranking curves; TKIs, tyrosine kinase inhibitor; F, first-generation; S, second-generation; Bev, bevacizumab; CT, chemotherapy; Lin, Linsitinib.
See this image and copyright information in PMC

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