Antitumoral activity of tyrosine kinase inhibitors in patients with non-small cell lung cancer harbouring rare epidermal growth factor receptor mutations.

Abstract

Mutations in the epidermal growth factor receptor (EGFR) have been reported as predictive markers of tumour response to tyrosine kinase inhibitors (TKIs) in patients with non-small cell lung cancer (NSCLC). Although the "common" EGFR mutations have been associated with response to EGFR-TKIs, the correlation with response to treatment for many other rare mutations is still unclear. The aim of this study was to investigate the clinical significance of rare and complex mutations, and the efficacy of EGFR-TKIs in this selected group of patients. Three hundred and thirty patients with stage IIIB/IV NSCLC (106 females aged 62.5±1.1years; 224 males aged 68.0±0.6years) were enrolled in the study. Formalin fixed paraffin embedded tissue samples were screened for mutations using a high resolution melting technique, followed by Sanger sequencing of exons 18-21 of the EGFR-gene. Mutation status was also tested using the Roche Cobas(®) EGFR mutation test. EGFR mutations were detected in 31 tumours (9.4%). Eleven cases carried novel mutations, six of these patients were treated with erlotinib or gefitinib. A response rate (RR) of 50.0% was obtained in the group with rare EGFR mutations, the PFS was 3.0months [standard deviation (STD)=5.4months]. The RR to EGFR-TKIs in patients with conventional EGFR mutations was 85% with a median PFS of 10.5months (STD=3.6months). We reported six patients with rare EGFR mutations of unknown clinical significance and their association with EGFR-TKIs. Report of cases harbouring rare mutations can support the decision making progress in this subset of patients.