Acquired multiple EGFR mutations-mediated resistance to a third-generation tyrosine kinase inhibitor in a patient with lung adenocarcinoma who responded to afatinib: A case report and literature review

For patients with advanced non-small cell lung cancer (NSCLC) that have epidermal growth factor receptor (EGFR) mutations, EGFR tyrosine kinase inhibitors (TKIs) are the standard treatment and have significant clinical benefits. Third-generation TKIs, such as osimertinib, almonertinib and furmonertinib, are effective for the treatment of NSCLC that is EGFR-sensitizing mutation-positive and T790M-positive. Despite the efficacy of third-generation TKIs, patients inevitably develop resistance and the resistance mechanisms are heterogeneous. Second-generation inhibitors, such as afatinib, may be crucial in treating diseases that have developed resistance to first- or third-generation inhibitors. However, the clinical effect of afatinib in patients with acquired multiple EGFR mutations is not well defined. To the best of our knowledge, the present report describes the first case of a patient with lung adenocarcinoma who had multiple co-existing EGFR resistance mutations, including EGFR L718Q, EGFR C797S, EGFR C797G, EGFR L792H, EGFR V802F and EGFR V689L. These mutations conferred resistance to almonertinib, whilst maintaining sensitivity to afatinib.