Therapeutic exploration of uncommon EGFR exon 20 insertion mutations in advanced non-small cell lung cancer: breaking through brambles and thorns.

Abstract

EGFR exon 20 insertion (EGFR ex20ins) mutations account for about 10-12% of all EGFR-mutated tumors, which are usually associated with primary drug resistance to conventional EGFR-TKI therapy and worse survival outcomes, and are currently a major problem for clinicians in clinical management. In recent years, with the rapid improvement of sequencing technology and careful review of clinical data, investigators have gained a deeper understanding and clearer cognition of the clinicopathological features and molecular mechanisms of these EGFR ex20ins mutations. The aim of this study was to systemically review the molecular structure and clinical characteristics of EGFR ex20ins mutations, and focus on summarizing the latest data of emerging therapies (including novel small-molecule EGFR-TKI drugs, specific monoclonal antibodies, novel drugs targeting other mechanisms, and immunotherapy) for those patients. Advances in overcoming these systemic challenges have greatly accelerated the development of new drugs targeting EGFR ex20ins, and are committed to designing more rational combination therapies to overcome or delay the emergence of drug resistance, ultimately improve the prognosis of such uncommon mutant populations.