Treatment outcomes with tyrosine kinase inhibitors in patients with uncommon EGFR mutations in non-small cell lung cancer: A multi-centre retrospective analysis.

Abstract

e20678 Background: The clinical significance of common epidermal growth factor receptor (EGFR) mutations (exon 19 deletions and exon 21 L858 mutations) in non-small cell lung cancer is well known1. However, 2-8% of NSCLC patients harbour an uncommon EGFR mutation2. Prognosis and response to tyrosine kinase inhibitors (TKIs) is unclear in this subgroup. The most frequent uncommon EGFR mutations are exon 18 G719 and exon 21 L861. Although not frequently reported, these appear to have favourable outcomes with TKIs3. Methods: We conducted a retrospective review of all patients with uncommon EGFR mutations identified at laboratories in 4 UK centres, between 2012 and 2016. Patient’s not treated with a TKI were excluded. Techniques including cold PCR were in use at contributing laboratories. The T790M resistance mutation was excluded from our study. For patients with uncommon EGFR mutations, patient characteristics and response to TKIs were analysed. Results: 29 patients with uncommon EGFR mutations, with both rare point mutations (86%) and deletions (14%), were identified. All patients were treated with a TKI. Age ranged from 37 to 85 (median 67). The majority (86%) of patients were performance status 1. TKIs used were afatinib (31%), gefitinib (24%) and erlotinib (45%). 19 patients (66%) benefitted from TKI treatment (38% partial response (PR), 28% stable disease (SD). 10 patients (34%) did not respond, including all four with exon 20 mutations. 15 mutations were exon 18 G719 mutations: 40% had a PR and 40% stable disease with TKI therapy. There were two L861 mutations, both responded with a PR. 13 patients remained on TKI treatment at data cut off. The median progression free survival at this time was 8.1months. Tabulated details of response according to mutation will be presented. Conclusions: The majority (66%) of NSCLC patients with uncommon EGFR mutations benefitted from TKI therapy in this series. These high clinical benefit rates, typified by patients with G719 mutation, are in line with the limited previous reports 1,3. Exon 20 mutations were associated with TKI resistance, in line with the literature4.