Acquired resistance to EGFR tyrosine kinase inhibitors in EGFR mutant lung cancer: Distinct natural history of patients with tumors harboring the T790M mutation

摘要: Purpose: Patients with epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma develop acquired resistance to EGFR tyrosine kinase inhibitors (TKI) after a median of 10 16 months. In half these cases, second mutation, T790M, underlies resistance. We undertook this study examine the clinical course patients harboring T790M mutation following progression on TKI. Experimental Design: EGFR-mutant cancer TKIs were identified as part prospective rebiopsy protocol in which postprogression tumor specimens collected for molecular analysis. Postprogression survival and characteristics disease compared without T790M. Results: initial from 58 93 (62%, 95% CI: 52–72). was more common biopsies lung/pleura tissue lymph nodes than distant sites ( P = 0.014). Median months (interquartile range 9–29 months); had significantly longer 0.036). often progressed previously uninvolved organ system 0.014) exhibited poorer performance status at time 0.007). Conclusions: Among TKIs, presence defines subset relatively favorable prognosis indolent progression. Knowledge is therefore important both care optimal design interpretation trials setting. Clin Cancer Res; 17(6); 1616–22. ©2010 AACR .