Potential treatment strategy for the rare osimertinib resistant mutation EGFR L718Q

The incidence of mutations in the epidermal growth factor receptor (EGFR) gene is about 50% in non-small cell lung cancer (NSCLC) patients in China (1). In the era of rapidly developing targeted therapies, the prognosis of advanced NSCLC has significantly improved, owing to the wide use of EGFR tyrosine kinase inhibitors (TKIs). Meanwhile, the emergence of de novo or secondary resistant mutations is a great clinical challenge. One of the novel resistant mutations, EGFR L718 substitutions (with the L718Q mutation being dominant clone), was reported to be identified in 8% of the osimertinib-resistant Chinese NSCLC patients (2). It has been revealed that EGFR L718Q independently leads to osimertinib resistance by stabilizing its non-reactive conformation (3). However, no report has yet identified how to effectively treat this rare mutation