Use of the epidermal growth factor receptor inhibitors gefitinib, erlotinib, afatinib, dacomitinib, and icotinib in the treatment of non-small-cell lung cancer: a systematic review

Introduction This systematic review addresses the use of epidermal growth factor receptor (EGFR) inhibitors in three populations of advanced non-small-cell lung cancer (NSCLC) patients-unselected, selected, and molecularly selected-in three treatment settings: first line, second line, and maintenance. Methods Ninety-six randomized controlled trials found using the MEDLINE and EMBASE databases form the basis of this review. Results In the first-line setting, data about the efficacy of EGFR tyrosine kinase inhibitors (TKIS) compared with platinum-based chemotherapy are inconsistent. Results from studies that selected patients based on clinical characteristics are also mixed. There is high-quality evidence that an EGFR TKI is preferred over a platinum doublet as initial therapy for patients with an activating mutation of the EGFR gene. The EGFR TKIS are associated with a higher likelihood of response, longer progression-free survival, and improved quality of life. Multiple trials of second-line therapy have compared an EGFR TKI with chemotherapy. Meta-analysis of those data demonstrates similar progressionfree and overall survival. There is consequently no preferred sequence for second-line EGFR TKI or second-line chemotherapy. The EGFR TKIS have also been evaluated as switch-maintenance therapy. No molecular marker could identify patients in whom a survival benefit was not observed; however, the magnitude of the benefit was modest. Conclusions Determination of EGFR mutation status is essential to making appropriate treatment decisions in patients with NSCLC. Patients who are EGFR mutation-positive should be treated with an EGFR TKI as first-line therapy. An EGFR TKI is still appropriate therapy in patients who are EGFR wild-type, but the selected agent should be administered as second- or third-line therapy.