Molecular characteristics and clinical outcomes of EGFR exon 19 indel subtypes to EGFR TKIs in NSCLC patients

Abstract

Patients with non-small cell lung cancer (NSCLC) with activating epidermal growth factor receptor (EGFR) mutations (exon 19 deletions and L858R) benefit from EGFR tyrosine kinase inhibitors (TKIs). However, some researchers have reported that responses to TKIs differ by subtypes of EGFR exon 19 mutations. We retrospectively analyzed EGFR exon 19 deletion subtypes and their correlation with clinical outcomes of treatment with TKIs. A cohort of 2664 consecutive patients with NSCLC was enrolled. A total of 440 EGFR exon 19 deletions were defined as 39 subtypes. Among them, 158 patients with advanced lung adenocarcinoma with EGFR exon 19 deletion mutations received EGFR-TKIs. There were no significant differences in progression-free survival or overall survival among patients with non-LRE deletions, delE746, or delL747 (P = 0.463 and P = 0.464, respectively). Furthermore, two patients with EGFR exon19 insertion had durable response to EGFR-TKIs. In conclusion, EGFR exon 19 is highly fragile, resulting in many different deletion and insertion subtypes. There were no significant differences in clinical outcomes after TKI treatment across the different subtypes. It is necessary to attempt to identify all patients with exon 19 deletions so that they can be offered TKI treatment.