OBJECTIVES : Lung cancer is one of the most common cancers and a worldwide health burden, with 2.1 million new cases reported globally in 2018. The aim of this study was to conduct a network meta-analysis (NMA) utilizing updated/mature randomized controlled trial (RCT) results for overall survival (OS) to examine the efficacy of first-line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) comparators for the treatment of EGFR mutation positive (EGFR+) non-small cell lung cancer (NSCLC). An NMA of EGFR-TKI comparators was previously conducted and published. This updated NMA includes the latest published OS data for dacomitinib and osimertinib.

METHODS : Eleven electronic databases were systematically searched for RCTs of first-line EGFR-TKI therapies that measured OS. Bayesian NMA was used to compare OS among patients receiving afatinib, dacomitinib, erlotinib, gefitinib, and osimertinib in the overall EGFR+ NSCLC population and in subgroup analyses by ethnicity (Asian and non-Asian) and by EGFR mutational status (exon 19 deletion or exon 21 L858R substitution mutations).

RESULTS : Based on the NMA dacomitinib demonstrated statistically significant improvement in OS versus gefitinib (hazard ratio (HR): 0.75, 95% credible interval (CrI): 0.59-0.95). Dacomitinib trended toward improved OS versus afatinib (HR:0.87, CrI: 0.61-1.24) and erlotinib (HR: 0.79, CrI: 0.44-1.42), and had comparable OS to osimertinib (HR: 0.94, CrI: 0.69-1.29). In addition, dacomitinib had the highest probability of being ranked first in the network (50.1%) followed by osimertinib (24.6%).

CONCLUSIONS : Dacomitinib trended towards improved OS compared to other EGFR-TKIs and had the highest probability of being ranked first in the network. Therefore, dacomitinib should be considered as one of the standard first-line treatment options for patients diagnosed with advanced EGFR+ NSCLC.