Epidemiological characteristics and therapeutic advances of EGFR exon 20 insertion mutations in non-small cell lung cancer

Abstract

The third most prevalent type of epidermal growth factor receptor (EGFR) mutation, EGFR exon 20 insertions (EGFRex20ins), involves 2%-12% of all cases of EGFR-positive non-small cell lung cancer (NSCLC). Approximately 90% of the mutations occur within the loop structure region, and the most frequently reported subtypes are A767_V769dup and S768_D770dup, which together account for almost 50% of instances. Apart from the unique subtype of A763_Y764insFQEA, NSCLCs with EGFRex20ins are resistant to approved EGFR tyrosine kinase inhibitors (TKIs) and are also insensitive to chemotherapy or immunotherapy. A new modality of treatment for NSCLC patients with EGFRx20ins has been established with the approval of mobocertinib and amivantamab. There are also numerous novel targeted treatments for NSCLC with EGFRex20ins in development, which are anticipated to improve this patient population's survival even further. This review provides a reference for the clinical management of these patients by summarizing the most recent epidemiological, and clinicopathological characteristics, diagnostic techniques, and therapeutic advances of EGFRex20ins in NSCLC.

Keywords: EGFR exon 20 insertions; epidemiology; non-small lung cancer; targeted therapy.