Osimertinib therapy in a 63-year-old woman with advanced adenocarcinoma of the lung that originally manifested with a sensitizing epidermal growth factor receptor (EGFR) L858R mutation and initially responded well to first-line erlotinib therapy. (a) CT image obtained after 15 months of erlotinib therapy shows progression of tumor, with development of multiple new lung nodules in the right lung base (arrows). The patient started osimertinib therapy for acquired resistance to erlotinib. Rebiopsy of the right lower lobe nodule confirmed the presence of a T790M mutation. (b) Follow-up CT image obtained after 2 months of osimertinib therapy shows a near-complete resolution of the nodules, representing a marked response to osimertinib. (c) However, on a CT image obtained at 10 months of osimertinib therapy, a growth of one of the nodules in the right lower lobe (arrow) is noted, indicating progressing tumor despite osimertinib treatment. (d) CT image obtained for further follow-up at 11 months after the initiation of osimertinib shows further growth of the dominant recurrent tumor (arrow), as well as an increase in smaller lung nodules in the right lower lobe, indicating the development of acquired resistance to osimertinib.