Dual EGFR and ABL Tyrosine Kinase Inhibitor Treatment in aPatient with Concomitant EGFR-Mutated Lung Adenocarcinomaand BCR-ABL1-Positive CML

Tyrosine kinase inhibitor (TKI) combination is expected to increase in the era of precision medicine. TKI combination may berequired to treat double primary cancers, each having a targetable gene, or to treat a single malignancy with multiple targetablegenes. Here, we demonstrate thefirst report of dual EGFR and ABL TKI treatment in a patient with concomitant EGFR-mutated lung adenocarcinoma and BCR-ABL1-positive chronic myeloid leukemia (CML). A 60-year-old man with an 8-yearhistory of CML was diagnosed as advanced EGFR-mutated lung adenocarcinoma. Complete molecular response of CML hadbeen achieved by imatinib, and ABL-TKI had been switched to nilotinib four years previously due to muscle cramps. Wediscontinued nilotinib and started afatinib. Although partial response of lung adenocarcinoma was achieved, cytogenetic relapseof CML was observed following nilotinib discontinuation. We applied the previously described framework of cytochrome P4503A4-mediated oral drug-drug interactions and selected gefitinib and nilotinib to treat both malignancies. We effectively andsafely administered this combination for seven months. The present report is thefirst to demonstrate the safety and efficacy ofdual EGFR and ABL TKI treatment in a patient with concomitant EGFR-mutated lung adenocarcinoma and CML.