Predictors of outcome for patients with lung adenocarcinoma carrying the epidermal growth factor receptor mutation receiving 1st-line tyrosine kinase inhibitors: Sensitivity and meta-regression analysis of randomized trials

Abstract

Purpose: We performed a sensitivity and meta-regression analysis, cumulating all randomized trials exploring the benefit of afatinib, erlotinib and gefitinib versus chemotherapy in advanced EGFR mutant NSCLC, to investigate the potential role of additional clinico-pathological predictors of TKIs efficacy.

Results: With regard to progression-free survival (PFS), a significant interaction according to ethnicity (Asian versus Caucasian versus mixed) and to trial design (retrospective versus prospective EGFR analysis), was found; a trend toward significance with regard to type of drug (gefitinib versus erlotinib versus afatinib) was determined. No statistically significant differences in survival were observed. With regard to response, a significant interaction according to ethnicity, trial design and type of drug, was found.

Conclusion: These data, together with a deeper characterization of the molecular background sustaining the oncogenic process, may contribute to create a clinico-pathologic predictive model, aimed to improve the magnitude of benefit expected from the use of targeted agents.

Keywords: Afatinib; Erlotinib; Ethnicity; Gefitinib; Lung cancer; Meta-analysis; Trial design.