Fig. 1

a Clinical course of this case. b Changes in chest CT images and T790M status. The upper and lower images show the upper and lower lobes, respectively. The narrow black arrow indicates the nodule in the upper lobe of the right lung at diagnosis; the first biopsy was performed in this nodule in September 2014, which was diagnosed as EGFR Ex19del-positive and T790M-negative adenocarcinoma according to the cobas^® test. The nodule in the upper lobe of the right lung shrank after gefitinib treatment and then increased again. The second biopsy was performed in August 2015 in the nodule indicated by the thick red arrow, which was diagnosed as EGFR Ex19del-positive and T790M-negative adenocarcinoma according to the cobas^® test. A new nodule appeared as a resistant tumor in the lower lobe of the left during gefitinib treatment (blue arrow), and this nodule increased after CDDP + PEM + BEV treatment. The third biopsy was performed in January 2016 in the nodule indicated by the orange arrow, which was diagnosed as EGFR Ex19del-positive and T790M-negative adenocarcinoma according to the cobas^® test. The mass in the lower lobe of the left lung had increased and multiple small nodules had appeared after EGFR-TKI re-challenge with E + BEV. The fourth biopsy was performed in the mass indicated by the green arrow, which was diagnosed as adenocarcinoma positive for both EGFR Ex19del and T790M according to the cobas^® test. The lesions improved after initiation of osimertinib treatment. The T790M AFs are shown in the graph below. T790M#, WT20#, Ex19del#, and WT19# refer to the copy numbers of the EGFR T790M mutation, no T790M in EGFR exon 20, deletion in EGFR exon 19, and no deletion in EGFR exon 19, respectively. CT computed tomography, EGFR epidermal growth factor receptor, CDDP cisplatin, PEM pemetrexed, BEV bevacizumab, TKI tyrosine kinase inhibitor, E erlotinib, AF allele frequency