EGFR exon 20 insertion mutations in non-small cell lung cancer

Mutations in the epidermal growth factor receptor (EGFR) gene are the most common targetable genomic drivers of non-small cell lung cancer (NSCLC). 90% of the EGFR mutations comprise of EGFR exon 19 deletion and exon 21 L858R mutation, while EGFR exon 20 insertion (EGFR Ex20Ins) is the third most common type of EGFR mutation. Currently, studies on EGFR Ex20Ins are relatively scarce and limited. The frequency of EGFR Ex20Ins mutations in NSCLC was 1-10%. Patients harboring EGFR Ex20Ins exhibited similar clinical characteristics except for poorer prognosis as compared to patients with sensitizing mutations in EGFR. Conventional TKIs have poor efficacy in a majority of EGFR Ex20Ins subtypes. Chemotherapy remains the preferred treatment for advanced NSCLC patients harboring EGFR Ex20Ins. However, some novel inhibitors are considered as putative candidates. This review focuses on the structural and biochemical features, clinical characteristics, treatments, and prognosis of EGFR Ex20Ins in NSCLC.