‘Classical’ but not ‘other’ mutations of EGFR kinase domain are associated with clinical outcome in gefitinib-treated patients with non-small cell lung cancer

Abstract

‘Classical’ mutations in the EGFR tyrosine kinase domain (exons 18, 19 and 21) have been associated with sensitivity to tyrosine kinase inhibitors (TKIs) in patients with NSCLC. The aim of the current study was to evaluate whether other than the classical G719X, DEL19 and L858R mutations of EGFR confer sensitivity to TKIs. Genomic DNA was extracted from microdissected formalin-fixed paraffin-embedded tumour tissue from 86 patients treated with gefitinib. Exons 18, 19 and 21 were amplified and subjected to direct sequencing. Eleven (13%) patients harboured the classical exon's 18, 19 and 21 mutations, while 14 (16%) had ‘other’ variants. There was a significantly higher percentage of ‘never-smoker’ patients with ‘classical’ EGFR mutations (P=0.002). Among patients with ‘classical’ mutations 3 patients achieved PR and 7 SD, while in the ‘other’ mutations group 10 patients had SD as best response. In the wild-type group, there were 3 patients with PR and 25 with SD. Median TTP was 16, 64 (P=0.002) and 21 weeks and median survival was 36, 78 and 67 weeks for patients with wild-type, ‘classical’ and ‘other’ EGFR mutations, respectively. The clinical relevance of ‘other’ EGFR mutation variants remains uncertain and requires further assessment in a prospective study.