Advances in the management of non-small-cell lung cancer harbouring exon 20 insertion mutations.

Epidermal growth factor receptor () mutation is one of the key oncogenic mutations in non-small-cell lung cancer with adenocarcinoma histology. Exon 19 deletions and exon 21 L858R substitutions account for 90%, while exon 20 insertions constitute 4-10% of mutations and are the third most prevalent activating mutations. exon 20 insertions are associated with decreased sensitivity to EGFR tyrosine kinase inhibitors and, until recently, effective targeted therapy against these tumours remained an unmet clinical need and chemotherapy was the only treatment of choice available. The approval of amivantamab and mobocertinib for patients who have progressed after chemotherapy represents an important step forward in the management of these patients. Here in this review, we summarize the epidemiology, structure and the tumour microenvironment of exon 20 insertion and also review the systemic treatments, including targeted therapies and ongoing clinical trials in exon 20 insertion mutations, as well as detection methods for exon 20 insertion. Lastly, resistant mechanisms and future directions are addressed.