EP1.14-26 Uncommon EGFR Mutations Sensitive to First-Generation EGFR-TKI, Icotinib

Abstract

The first-generation EGFR-TKIs are the standard of care for non-small cell lung cancer patients withEGFR activating mutations. Patients with EGFR L858R (p.L858R) or exon 19 deletions are the most prevalent subgroup sensitive to EGFR-TKIs. Previous reports showed that the minority of lung cancer patients with rare EGFR mutations still achieved clinical benefit with EGFR-TKIs. Here, we profiled the landscape of gene mutations in lung cancer patients who responded to Icotinib (a first- generation EGFR-TKI approved in China) treatment without classic EGFR activating mutations. We performed a comprehensive sequencing study by a NGS-based panel on a cohort of eleven lung adenocarcinoma patients without common EGFR sensitive mutations and receiving Icotinib treatment in a previous clinical trial (ICOGEN, NCT01040780). The pre-treatment FFPE tissues from all eleven patients were sequenced using a 500-gene panel. Six patients responded to Icotinib treatment including three patients with partial response (PR) and three patients with stable disease (SD). The other five patients showed immediate disease progression (PD) after the treatment of Icotinib. Rare EGFR mutations in the EGFR tyrosine kinase domain, including EGFR mutations W731C (exon 19), M793I (exon 20), and V845L (exon 21), were detected in the PR and SD groups but not in the PD group. EGFR somatic mutation M793I has been detected in the lung tissue of a patient according to the COSMIC record (COSM1716335). In the PR and SD groups, ERBB2 I655V and JAK2 R215Q were identified as potential mutations which could relate to Icotinib sensitivity. This study uncovered potential new biomarkers predicting the clinical benefit to Icotinib. With further validation and evidence, it may expand the current patient populations which benefits from the first-generation EGFR-TKIs.