The median survival of ERSA (gefitinib tablets) is 10 months. According to clinical observation, the average time of drug resistance of ERSA is about 1 year, some of the earlier ones have developed resistance in 6 months, some of the late ones have not developed resistance after 1.5 years or 2 years of drug use, but the proportion is extremely low, and there are even those who have used the drug for 5 years. The individual differences are quite large. However, most of them will develop resistance within 1 year. How to determine if ERSA is resistant (still effective) Drug resistance will occur with most drugs, but it may occur earlier or later, and ERSA is no exception for lung cancer treatment. The relationship between efficacy and duration of drug use can be compared with this line graph of efficacy and duration of drug use. This icon does not represent the real situation of efficacy and duration of drug use, but only serves as a visual analogy for easy understanding. In general, for patients with effective treatment, the first three months of ERSA use, the patient feels the best in terms of symptom improvement and mental outlook. After 3 months, the patient enters into a plateau period. During this period of time, ERSA is still effective, “neither good nor bad”, the tumor is no longer shrinking, no bigger, no metastasis, and the disease is relatively stable, which we call plateau period. After the plateau period, the disease enters the progressive drug resistance period, which starts gradually and requires a time process, called incomplete drug resistance period. After the incomplete drug resistance period, it will enter the complete drug resistance period, and it will be completely ineffective. Therefore, when you enter the incompletely resistant stage, we should pay attention to it, take early measures, actively treat it and control the progress of the disease. The most important question for patients after taking Erythroxa and Troche is the cause of drug resistance. What is the most effective treatment option after drug resistance? The vast majority of people cast their focus on what to do after drug resistance? In fact, there are very few remedies after drug resistance, and the clinical efficacy has not been confirmed or is poor. So shouldn’t we be more concerned about what options are available to delay resistance or find an alternative therapy before it becomes resistant after Eretzac or Troche is effective? In acquired resistance after EGFR TKI treatment failure, it is thought that about 50% are T790M mutations and about 20% are c-MET gene amplification, and the rest are not yet clear about the specific resistance mechanism. Some of the methods commonly used at present after Erythroxa or Troche resistance, I will list them here. 1, chemotherapy: Lipitor + platinum 2, pazopanib or doxorubicin 3, vandetanib 4, afatinib 5, cetuximab 6, afatinib + cetuximab A global first phase II clinical study of afatinib in combination with cetuximab in patients with positive T790M mutations, with ORR as the primary study endpoint. The results showed that of the 53 patients enrolled, 48 (90.6%) achieved disease control, with a confirmed ORR of 52.8% (28/53) in patients with evaluable efficacy, and an ORR of 54.5% (18/33) in T790M mutation-positive patients, with one case achieving complete remission. The patients were well tolerated. This phase II study also seems to suggest that a combination regimen that targets both the extracellular portion of EGFR (cetuximab) and a highly selective new intracellular mutation (T790M mutation, afatinib) for acquired resistance in NSCLC caused by T790M mutation provides a new therapeutic idea to overcome resistance to first-generation EGFR TKI and may result in better outcomes than afatinib alone. The above regimens are personally preferable to 3 and 6. The above regimens are personally preferable to 3 and 6, while other regimens have lower clinical efficacy. After drug resistance, it is important to distinguish the nature of the occurrence of drug resistance. 1, if only the primary foci, intrapulmonary metastases, lymph gland enlargement, and the scale of enlargement is very small, then it is recommended not to discontinue all of ERSA, because it is only partially resistant. At this time, you can continue to take ERSA with other treatments. For example, it is generally recommended that patients in this state be treated with a single drug, Lipitor, in combination with ERSA. If the patient is completely off of ERSA and on chemotherapy, it is necessary that the patient has had effective chemotherapy or that the patient has never had chemotherapy, in which case discontinuation of ERSA for chemotherapy should be considered. If the patient has a history of chemotherapy and the results are poor, it is important to discontinue ERSA completely. Even if the patient has a history of effective chemotherapy, it is important to pay attention to what kind of regimen the patient has used. If the chemotherapy drugs have almost been used, and the first-line and second-line chemotherapy regimens have been used, it is also prudent to discontinue the targeted drugs completely. Because cancer cells are resistant to targeted drugs, they are also resistant to chemotherapy drugs. 2.Only elevated tumor markers are not a criterion for discontinuation of Erythromycin. It is disapproved that some patients are eager to stop ERSA and take chemotherapy after CEA rises and imaging does not confirm drug resistance. However, there are exceptional ones. For example, a patient was on ERSA straight away at the start of the disease and showed a rise in CEA a year and a half later. At that time, the patient was asked to take ERSA for another month and follow up CEA+chest CT, but the chest CT did not change much, and the CEA increased linearly, showing signs of drug resistance. Because the patient had not been treated with chemotherapy, it was recommended to discontinue ERSA and go directly to chemotherapy. After four standard chemotherapy treatments, the CEA dropped by a large margin and the chest CT image was stable. Later, he continued to take ERSA and his status was still very good. Although the CEA went up a bit later, but it is an acceptable range, the key is good status + stable imaging. 3.If new metastases appear, when should I stop taking ERSA? (1) If there is an isolated metastasis, you can actively treat the metastasis and continue to take the targeted drug at the same time. (2) If there are multiple metastases, consider that the drug resistance is strong and stop the targeted drug, then chemotherapy is recommended. If chemotherapy fails, the patient can use the targeted drugs again, and sometimes they can still be effective. 4.If targeted therapy is effective in the early stage and then new metastatic lesions appear later, or new progression, based on the principle of tumor heterogeneity, it may be a new lung cancer lesion caused by the proliferation of cancer cells without EGFR mutation, but the tumor cells with EGFR mutation are still inhibited by targeted drugs. At this time, if the targeted drug is discontinued, it will lead to further proliferation of the original EGFR mutated cancer cells inhibited by the targeted drug, and these EGFR mutated lung cancer cells are often the vigorous and highly malignant part, which are prone to further metastasis or progression. Therefore, for, the treatment after targeted drug resistance must be cautious and cannot be easily stopped by oneself. In the past, there were some patients who had rapid disease progression after stopping the drug, leading to adverse consequences.