New advances in the treatment of EGFR exon20ins mutant advanced NSCLC.

Abstract

The epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutations, albeit less frequent, are a clinically significant subset within the EGFR mutation landscape of non-small cell lung cancer (NSCLC), accounting for roughly 4%-12% of all EGFR-altered cases. Ranking as the third most prevalent EGFR mutation type, these ex20ins mutations trail the widely recognized EGFR exon 19 deletion (19-Del) and exon 21 L858R substitution. In advanced-stage NSCLC patients with EGFR exon 20 insertion mutations, conventional treatments such as EGFR tyrosine kinase inhibitors (TKIs), chemotherapy, and immunotherapies often yield suboptimal responses, resulting in unfavorable clinical outcomes. This unmet clinical need underscores the urgency to explore innovative targeted therapies. In the realm of precision medicine, targeted agents specifically tailored for EGFR ex20ins mutations have emerged as promising candidates. This review examines the latest research on targeted therapies for EGFR ex20ins mutations, dissecting the mechanisms of action of these agents, evaluating the results of relevant clinical trials, and integrating the evidence in a systematic manner. The aim is to uncover novel therapeutic insights and strategies to optimize the clinical management of patients with EGFR ex20ins mutation-positive NSCLC.