Abstract
BACKGROUND: Through deeper understanding of targetable driver mutations in non-small-cell lung cancer (NSCLC) over the past years, some patients with driver mutations have benefited from the targeted molecular therapies. Although the anaplastic lymphoma kinase and BRAF mutations are not frequent subtypes in NSCLC, the availability of several targeted-drugs has been confirmed through a series of clinical trials. But little is clear about the proper strategy in rare BRAF G469A mutation, not to mention co-exhibition of anaplastic lymphoma kinase and BRAF G469A mutations, which is extremely rare in NSCLC. CASE SUMMARY: We present a patient to stage IVA lung adenocarcinoma with coexisting echinoderm microtubule associated protein like-4 rearrangement and BRAF G469A mutation. She received several targeted drugs with unintended resistance and suffered from unbearable adverse events. CONCLUSION: Due to the rarity of co-mutations, the case not only enriches the limited literature on NSCLC harbouring BRAF G469A and echinoderm microtubule associated protein like-4 mutations, but also suggests the efficacy and safety of specific multiple-drug therapy in such patients.