Background The epidermal growth factor receptor (EGFR) signaling pathway is crucial for regulating tumorigenesis and cell survival and may be important in the development and progression of non-small cell lung cancer (NSCLC). We examined the impact of EGFR-tyrosine kinase inhibitors (TKIs) on progression-free survival (PFS) and overall survival (OS) in advanced NSCLC patients with and without EGFR mutations.MethodsRandomized trials that compared EGFR-TKIs monotherapy or combination EGFR-TKIs-chemotherapy with chemotherapy or placebo were included. We used published hazard ratios (HRs), if available, or derived treatment estimates from other survival data. Pooled estimates of treatment efficacy of EGFR-TKIs for the EGFR mutation-positive (EGFRmut +) and EGFR mutation-negative (EGFRmut-) subgroups were calculated with the fixed-effects inverse variance weighted method. All statistical tests were two-sided.ResultsWe included 23 eligible trials (13 front-line, 7 second-line, 3 maintenance; n = 14570). EGFR mutation status was known in 31% of patients. EGFR-TKIs treatment prolonged PFS in EGFRmut + patients, and EGFR mutation was predictive of PFS in all settings: The front-line hazard ratio for EGFRmut+ was 0.43 (95% confidence interval [CI] = 0.38 to 0.49; P <. 001), and the front-line hazard ratio for EGFRmut- was 1.06 (95% CI = 0.94 to 1.19; P =. 35; P interaction <. 001). The second-line hazard ratio for EGFRmut + was 0.34 (95% CI = 0.20 to 0.60; P <. 001), and the second-line hazard ratio for EGFRmut- was 1.23 (95% CI = 1.05 to 1.46; P =. 01; Pinteraction <. 001). The maintenance hazard ratio for EGFRmut+ was 0.15 (95% CI = 0.08 to 0.27; P <. 001), and the maintenance hazard ratio for EGFRmut- was 0.81 (95% CI = 0.68 to 0.97; P =. 02; Pinteraction <. 001). EGFR-TKIs treatment had no impact on OS for EGFRmut+ and EGFRmut- patients.ConclusionsEGFR-TKIs therapy statistically significantly delays disease progression in EGFRmut+ patients but has no demonstrable impact on OS. EGFR mutation is a predictive biomarker of PFS benefit with EGFR-TKIs treatment in all settings. These findings support EGFR mutation assessment before initiation of treatment. EGFR-TKIs should be considered as front-line therapy in EGFRmut+ advanced NSCLC patients.
ASJC Scopus subject areas
- Cancer Research