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

Abstract

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][2][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.Mefatinib is a novel, second-generation EGFR-TKI with promising clinical efficacy and safety for patients with common EGFR mutations [8]. Here, we report the results of the phase II open-label, single-arm, multicenter study investigating the efficacy and safety of Mefatinib as firstline therapy for patients with NSCLC harboring uncommon EGFR mutations (ChiCTR2000029058).