OBJECTIVES: The field of EGFR-positive non-small cell lung cancer (NSCLC) is rapidly evolving with many new therapies entering the EU market over the past ten years. This study identified all first-line EGFR+ NSCLC treatments that received EU marketing authorization from 2007 onwards or that are currently under clinical investigation. In addition, comparative efficacy in terms of progression-free survival (PFS) and overall survival (OS) of those interventions and chemotherapy was determined.

METHODS: A systematic literature review (SLR) was conducted, in line with the PRISMA guidelines, to identify relevant clinical trials evaluating the efficacy of first-line EGFR+ NSCLC treatments. Comparability of study design, patient characteristics and reported outcomes of included publications were assessed in a feasibility assessment. A fixed effects NMA using a Bayesian framework was performed to compare PFS and OS for all included treatments.

RESULTS: In total, 25 studies were eligible for inclusion. During the feasibility assessment, six studies were excluded. Reasons for exclusion were: follow-up time <1 year (n=2), updated results available (n=2), results reported elsewhere (n=1), and no connection to the evidence network (n=1). Treatments considered in the NMA included afatinib, bevacizumab + chemotherapy, dacomitinib, erlotinib, erlotinib + bevacizumab, gefitinib, linsitinib + erlotinib, necitumumab, TG4010 + chemotherapy and chemotherapy. Most interventions improved PFS as compared to chemotherapy. The greatest increase in PFS was achieved with erlotinib + bevacizumab (hazard ratio: 0.39, 95% CrI 0.32 - 0.48). The OS analysis showed little evidence to differentiate between treatments of interest.

CONCLUSIONS: Most interventions improved PFS as compared to chemotherapy, with erlotinib + bevacizumab achieving the greatest improvement. The inability to distinguish between treatments in terms of OS is likely to be caused by the cross-over of comparative treatments in second line treatment.