Dacomitinib is an irreversible, oral small-molecule inhibitor of not only EGFR but also the entire ErbB family. Both dacomitinib and afatinib are classified as second-generation EGFR-TKIs (tyrosine kinase inhibitors). Afatinib was approved in 2013, prior to dacomitinib, which was approved later in 2018. In the meantime, osimertinib, a third-generation EGFR-TKI, was approved in 2015. Consequently, the position of dacomitinib in EGFR-TKI treatment is unclear due to the differences in approval timing. Recently, it has been reported that the efficacy of EGFR-TKI is predicted, not by which exon of the EGFR gene is mutated, but by the structural change in the EGFR protein due to the mutation. Here, we present an EGFR-mutated lung cancer patient with a long history of treatment, in which EGFR ex.19 deletion (E746_S752 > V) and G724S mutations were detected by liquid biopsy during afatinib resistance, and switching to dacomitinib showed improvement of cancerous meningitis. The optimal EGFR-TKI may be selected by understanding the EGFR compound mutation profile by next generation sequencing and predicting the effect based on the structure. Dacomitinib may be effective in afatinib-refractory carcinomatous meningitis.