Impact of Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor Treatment in Advanced Non-Small Cell Lung Cancer: A Meta-Analysis

ABSTRACT Background Previous meta-analyses have reported that epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) improves progression-free survival (PFS) in patients with advanced non-small cell lung cancer (NSCLC) harbouring EGFR mutation. We examined the influence of EGFR-TKI on PFS and overall survival (OS) in those with (EGFR+) and without mutation (EGFR-). Methods We included published and unpublished randomised trials of advanced NSCLC that compared EGFR-TKI monotherapy or combination EGFR-TKI chemotherapy with chemotherapy or placebo. We used published hazard ratios (HR) if available, or derived treatment estimates from other survival data. We investigated treatment effects in different treatment settings and trial regimens. Results We identified 20 eligible trials investigating EGFR-TKI in front-line (n = 12), second or subsequent (n = 5), and maintenance (n = 3) treatment, with EGFR status known in 3198 (23%) patients. Overall, HR for EGFR-TKI over control for PFS were (EGFR+) 0.37 (95% CI, 0.32 to 0.42; p Conclusions In this meta-analysis, treatment with EGFR-TKI was found to significantly delay disease progression in EGFR+ patients; however, no impact on OS was identified. EGFR mutation is a predictive biomarker of PFS benefit with EGFR-TKI treatment in all settings. These findings support assessment for EGFR mutation before initiation of EGFR-TKI treatment and that EGFR-TKI should be considered as front-line therapy in EGFR+ patients with advanced NSCLC. Disclosure R. Gralla: Consultant or advisory role for Boehringer Ingelheim. V. Hirsh: Advisory role for Boehringer Ingelheim. A. Inoue: Received lecture fees and research grants from AstraZeneca. C.J. Yang: Advisory roles for Boehringer Ingelheim, AstraZeneca, Roche and OSI, and have received honoraria from AstraZeneca, Roche and OSI. All other authors have declared no conflicts of interest.