Common EGFR-mutated subgroups (Del19/L858R) in advanced non-small-cell lung cancer: chasing better outcomes with tyrosine kinase inhibitors

Abstract

Ten years ago, somatic mutations in EGFR were identified in patients with non-small-cell lung cancer. Demonstration of the antitumor efficacy of EGF receptor-directed tyrosine kinase inhibitors resulted in their approval for the treatment of advanced non-small-cell lung cancer. Insights into the role of EGFR-sensitizing mutations and acquired and de novo T790M resistance mutations followed, and differences in progression-free survival for patients with EGFR Del19- and L858R-mutated tumors treated with reversible first-generation EGF receptor tyrosine kinase inhibitors were reported. Recently, overall survival benefit in patients with Del19- but not L858R-mutated tumors has been demonstrated after treatment with afatinib, an irreversible ErbB family blocker. Although the biology underlying this difference in survival is currently unclear, this review examines several hypotheses.

Keywords: Del19; EGFR; L858R; NSCLC; TKI; afatinib; chemotherapy; erlotinib; gefitinib; mutations.