EGFR mutations and EGFR tyrosine kinase inhibitors

Abstract

In 2004, three groups independently noted that the presence of activating mutations in patients with advanced non-small-cell lung cancer made tumours sensitive to EGFR tyrosine kinase inhibitors. 1 Tomida S Yatabe Y Yanagisawa K Mitsudomi T Takahashi T Throwing new light on lung cancer pathogenesis: updates on three recent topics. Cancer Sci. 2005; 96: 63-68 Crossref PubMed Scopus (20) Google Scholar Since then, nine randomised trials including almost 1800 patients have been done, which have compared chemotherapy with tyrosine kinase inhibitors for first-line treatment of a subpopulation of patients with advanced non-small-cell lung cancer tumours that contained these mutations. 2 Lee CK Brown C Gralla RJ et al. Impact of EGFR inhibitor in non-small cell lung cancer on progression-free and overall survival: a meta-analysis. J Natl Cancer Inst. 2013; 105: 595-605 Crossref PubMed Scopus (431) Google Scholar Clinical activity of afatinib in patients with advanced non-small-cell lung cancer harbouring uncommon EGFR mutations: a combined post-hoc analysis of LUX-Lung 2, LUX-Lung 3, and LUX-Lung 6Afatinib was active in non-small-cell lung cancer tumours that harboured certain types of uncommon EGFR mutations, especially Gly719Xaa, Leu861Gln, and Ser768Ile, but less active in other mutations types. Clinical benefit was lower in patients with de-novo Thr790Met and exon 20 insertion mutations. These data could help inform clinical decisions for patients with non-small-cell lung cancer harbouring uncommon EGFR mutations. Full-Text PDF Correction to Lancet Oncol 2015; 16: 747Torri V, Broggini M, Garassino MC. EGFR mutations and EGFR tyrosine kinase inhibitors. Lancet Oncol 2015; 16: 746–48—The seventh sentence of the final paragraph of this Comment should read: “Results for Leu858Arg are still inconclusive because although progression-free survival is higher in patients given all EGFR inhibitors versus chemotherapy, overall survival seems to be better with chemotherapy than with afatinib for these patients.” This correction has been made to the online version as of June 29, 2015, and the printed version is correct. Full-Text PDF