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Background. Tyrosine kinase inhibitors (TKIs) are the standard of treatment of EGFR-positive metastatic non-small cell lung cancer (mNSCLC). Different TKI generations have different properties. Currently there are no results of head-to-head clinical trials of II generation TKI afatinib against III generation TKI osimertinib. In such case network meta-analysis (NMA) can be used for evidence synthesis.&#x0D;Aim. To compare afatinib and osimertinib effect on overall survival (OS) in first-line drug treatment of EGFR-positive mNSCLC.&#x0D;Materials and methods. Search of trials to build evidence network was done in Medline, CT.gov, and EU-CTR. Endpoint was OS measured as hazard ratio (HR) of all-cause death. Analysis was split into base case analysis and two sensitivity analyses depending on criteria of transitivity. Random effect model was used for NMA. Results were analyzed in overall population and subgroups according to the type of EGFR-mutation, ECOG score, and presence of CNS metastases. Statistical analysis was done in R with netmeta package.&#x0D;Results. Fourteen trials were included in the study. There was no statistically significant difference regarding OS between afatinib and osimertinib in overall population neither in base case nor in first sensitivity analysis: HR 1.06 [0.79; 1.41], p=0.697 and 1.08 [0.83; 1.41], p=0.561, respectively. Results of comparison of II generation TKIs against osimertinib in second sensitivity analysis were consistent: HR 1.03 [0.81; 1.31], p=0.834. Results in all subgroups were consistent with each other and overall population. There was no statistically significant heterogeneity/inconsistency in the network in any of the analyses.&#x0D;Conclusion. Afatinib and osimertinib have similar efficacy regarding OS in first-line drug treatment of EGFR-positive mNSCLC.

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Comparison of afatinib and osimertinib effect on overall survival in first-line drug treatment of EGFR-positive metastatic non-small cell lung cancer: network meta-analysis