Update of data on effi cacy of reversible the EGFR tyrosine kinase inhibitors in patients with non-small cell lung cancer and common or rare activating mutations in EGFR gene

Abstract

Mutations in epidermal growth factor receptor (EGFR) gene are detected in approximately 10% of non-small cell lung cancer (NSCLC) patients of Caucasian origin and in 30–40% patients of eastern Asian origin. The most commonly found EGFR mutations in NSCLC include deletions in exon 19 (45–50% of all identified mutations) and L858R substitution in exon 21 (40–45% of all mutations). Rare mutations constitute approx. 10–15% of all known EGFR mutations, and include insertion in exon 20, G719X and E709X substitutions in exon 18, L861Q point mutation in exon 21 as well as T790M and S768I substitutions in exon 20. These mutations lead to changes of one or several aminoacids in EGFR tyrosine kinase (TK) protein domain. The types of mutations affects the level of tyrosine kinase activity and its conformation and also the efficacy of EGFR TK inhibitors (EGFR TKIs). Administration of EGFR TKIs in patients with tumours carrying common EGFR mutations (deletions in exon 19 and L858R substitution) is indicated as first-line treatment or, if that was not possible, as a second line therapy. The effect of EGFR TKIs therapy in tumours carrying L858R mutation is slightly worse than in cases with deletions in exon 19 of EGFR gene, which however should not exclude this line of therapy in patients with the former mutation. EGFR TKIs seem to be a good therapeutic option in tumours where G719X or L861Q substitution was identified as well as in patients with coexisting rare mutations (included T790M) and common ones. In other cases, available clinical data on the role of rare mutations in development of primary resistance to EGFR TKIs are too scarce. Patients carrying some insertion variants in exon 20 or S768I point mutation seem to have a lesser chance to respond to EGFR TKIs therapy. Therefore, management of patients with private mutations of EGFR gene should be subject to utmost individualisation.