In recent years, due to rapid advances in molecular biology and modern pharmacology, small molecule complex kinase inhibitors (TKIs) have played a large role in the treatment of lung cancer and other diseases, greatly improving the therapeutic outcome and prognosis of such patients. However, the majority of patients who are effective on TKIs develop drug resistance around 8-10 months, leading to disease progression. However, the choice of treatment after progression of TKIs is a big learning curve and should not be ignored! For patients with mutations in EGFR, there are three general scenarios of drug resistance after TKIs: 1) rapid overall progression with more new lesions or a significant increase in the size of the original lesions; 2) slow progression with no new lesions; 3) stable original lesions with new lesions, but limited new lesions. So in these three cases, how should one respond? For the first case, it is definitely necessary to change the drug, while for the second and third cases, a cautious decision is needed, sometimes it is necessary to enhance the local treatment while retaining the original treatment. For example, if an isolated metastasis in the brain occurs during the course of ERSA treatment, local treatment of the brain lesion, such as gamma knife treatment, is required, while continuing to apply ERSA treatment, so that the effective drug effect can be maximized.