Eligible patients received 3rd generation EGFR-TKIs (AZD9291 and AVITINIB) were enrolled into this study. Tumor tissue sample within 6 months, and 10ml periphereal blood samples were collected at baseline. After treatment initiation, 10ml periphereal blood would be collected at every image testing time point until disease progression. Blood samples will be draw using EDTA tube and centerfuged within 2 hours and store in -80 refrigerator.