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 (<i>EGFR</i>) 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 <i>EGFR</i> 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 <i>EGFR</i> resistance mutations, including <i>EGFR</i> L718Q, <i>EGFR</i> C797S, <i>EGFR</i> C797G, <i>EGFR</i> L792H, <i>EGFR</i> V802F and <i>EGFR</i> V689L. These mutations conferred resistance to almonertinib, whilst maintaining sensitivity to afatinib.