2025 Volume 65 Issue 2 Pages 71-79
EGFR exon 20 insertion mutations (EGFR Exon 20ins) account for 4-10% of all EGFR mutations. Unlike classical activating mutations such as exon 19 deletions and exon 21 L858R point mutations, EGFR Exon 20ins exhibit primary resistance to conventional EGFR-TKIs, leading to a generally poor prognosis. This has necessitated the urgent development of novel therapeutic approaches. Recent advances have shed light on the structural characteristics and mechanisms of therapeutic resistance associated with EGFR Exon 20ins. Amivantamab, a bispecific antibody targeting EGFR and MET, has been approved for the treatment of unresectable advanced or recurrent non-small cell lung cancer (NSCLC) with EGFR Exon 20ins in combination with chemotherapy. Furthermore, the efficacy of novel EGFR-TKIs specifically targeting EGFR Exon 20ins has been demonstrated in early clinical trials, offering promising new treatment options for patients with EGFR Exon 20ins-positive NSCLC. However, challenges remain, including the management of adverse events, evaluation of therapeutic efficacy across subtypes of EGFR Exon 20ins, effectiveness against central nervous system lesions, and elucidation of mechanisms of resistance. This provides an overview of the pathophysiology and current treatment landscape of EGFR Exon 20ins-positive NSCLC, as well as future therapeutic perspectives based on the latest evidence.
