A phase II study on Mefatinib as first-line treatment of patients with advanced non-small-cell lung cancer harboring uncommon EGFR mutations

Dear Editor,Uncommon mutations in exons 18-21 of the epidermal growth factor receptor(EGFR)gene account for 10%–15%of all EGFR mutations when considered as a whole group[1,2].However,each variant confers heterogeneous clinical outcomes to different generations of EGFR tyrosine kinase inhibitors(TKIs)with G719X,L861Q,and/or S768I showing adequate sensitivity to EGFR inhibition[1–3].Osimertinib,based on its superior survival outcomes,has become the preferred first-line treatment for patients diagnosed with advanced non-small cell lung cancer(NSCLC)harboring common EGFR mutations[4];however,its efficacy in patients harboring G719X,S768I,and/or L861Q mutations was comparable or even inferior to Afatinib[5].Afatinib,a second-generation EGFR-TKI,has received approval for extended clinical indication in treating previously untreated patients with metastatic NSCLC harboring G719X,L861Q,and/or S768I based on the findings from the pooled analysis of three clinical trials(LUX-Lung 2/3/6)[2].The real-world clinical efficacy of Afatinib for treating this patient subset has been consistently demonstrated by two large retrospective studies[6,7].In China,chemotherapy remains a standard first-line treatment for this patient subset,with Afatinib available only as an off-label treatment option.