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First-line tyrosine kinase inhibitors in EGFR mutation-positive non-small-cell lung cancer: a network meta-analysis

Authors Holleman MS, van Tinteren H, Groen HJM, Al MJ, Uyl-de Groot CA

Received 2 October 2018

Accepted for publication 24 January 2019

Published 20 February 2019 Volume 2019:12 Pages 1413—1421


Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Andrew Yee

Peer reviewer comments 2

Editor who approved publication: Dr Sanjeev Srivastava

Marscha S Holleman,1,2 Harm van Tinteren,3 Harry JM Groen,4 Maiwenn J Al,1,2 Carin A Uyl-de Groot1,2

1Erasmus School of Health Policy and Management, Erasmus University Rotterdam, Rotterdam, the Netherlands; 2Institute for Medical Technology Assessment, Erasmus University Rotterdam, Rotterdam, the Netherlands; 3Department of Biometrics, Netherlands Cancer Institute, Amsterdam, the Netherlands; 4Department of Pulmonary Diseases, University of Groningen and University Medical Center Groningen, Groningen, the Netherlands

Background: EGFR-tyrosine kinase inhibitors (EGFR-TKIs) including afatinib, dacomitinib, erlotinib, gefitinib, and osimertinib have proven efficacy in terms of progression-free survival (PFS) in patients with non-small-cell lung cancer (NSCLC) harboring EGFR mutations. However, an overall view for comparing efficacy and toxicity on a meta-level is lacking. This study compared efficacy and toxicity of first-line treatment with five different EGFR-TKIs by conducting a network meta-analysis (NMA).
Methods: A systematic review was performed, aiming to find eligible literature. Data of PFS, overall survival (OS), objective response rate (ORR), and adverse events were extracted. An NMA based on Bayesian statistics was established to synthesize the efficacy and toxicity of all treatments.
Results: Thirteen randomized controlled trials, including data from 3,539 patients with EGFR-mutated NSCLC, were analyzed. Rank probabilities showed that osimertinib had a potentially better efficacy in terms of PFS and OS compared to all other TKIs. For ORR, afatinib and osimertinib showed a trend of superiority compared to the other four TKIs. Furthermore, there was a high risk of diarrhea and rash for patients treated with afatinib or dacomitinib as well as a moderate risk for treatment with erlotinib, gefitinib, and osimertinib.
Conclusion: Our study showed a favorable efficacy of osimertinib in terms of PFS and OS compared to all other EGFR-TKIs in patients with NSCLC harboring activating EGFR mutations. Furthermore, gefitinib, erlotinib, and osimertinib were associated with fewer toxicities compared to the other TKIs. Therefore, osimertinib is indicated as a preferable first-line TKI in patients with activating EGFR-mutated NSCLC.

Keywords: EGFR-TKI, gefitinib, erlotinib, afatinib, osimertinib, network meta-analysis

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