Acquired T790M resistance do afatinib in EGFR mutated lung adenocarcinoma.

The patient was a 73-year-old female who had neversmoked and who had received a diagnosis of stage IVlung adenocarcinoma. In direct sequence method, the resected tumor specimen revealed Ex19 E746_A750del (deletion IN frame) 2235_2249del15 (Deletion). But T790M mutation was not detected in the specimen. This patient, not previouslytreated with gefitinib or erlotinib,had afatinib at a 40-mg dose. Uponstarting the drug administration, primary tumor and pulmonary metastases lesions responded well to the treatment. Eventually, however, 11 months after the initiation of afatinib therapy she developed a recurrent pleural metastaticnodules and increased pleural fluid that initially responded to afatinib (progressive free survival: 10 months). The T790M mutation, which were not present in the pretreatment tumor tissue, as well as the same Ex19 mutation as that found before treatment were identified in tumor cells from the pleural aspirate.