Keypoint: ADZ9291 and Rociletinib show a promising future for patients with advanced non-small cell lung cancer who have been treated with EGFR inhibitors and have mutations in the resistance gene EGFRT790M. The first generation EGFR inhibitors, gefitinib (ERSA) and erlotinib (Troche), have been clinically successful; however, with widespread clinical use, resistance has become an increasingly prominent problem, with most patients experiencing resistance within 1-2 years, and about 60% of patients have resistance mechanisms due to the occurrence of EGFRT790M mutations. The second generation EGFR inhibitors afatinib and daclatinib, afatinib can reduce the resistance gene EGFRT790M mutation, but its efficiency is low and fails to overcome the resistance generated by T790M mutation, and it ended in failure in phase III clinical. Daclatinib is in the process of development. ADZ9291 and Rociletinib, third-generation EGFR inhibitors, which target not only EGFR mutations but also advanced non-small cell lung cancer patients who have developed EGFRT790M mutations in the resistance gene. Two recent studies on ADZ9291 and Rociletinib, both published in the New England Journal, showed encouraging efficacy. The results of the ADZ9291 study showed that 253 patients with advanced non-small cell lung cancer treated with ADZ9291 drug (20-240 mg/day) had an ORR (objective response rate) of 51% and a DCR (disease control rate) of 84%. In the 222 dose escalation group, median PFS reached 8.2 months. ADZ9291 was significantly more effective in the T790M mutation group than in the no-mutation group, with an ORR of 61% vs. 21%, DCR of 95% vs. 61%, and median PFS of 9.6 months vs. 2.8 months. Moreover, there was no dose-limiting toxicity of AZD9291 treatment and no maximum tolerated dose was found. Its side effects rash (40%), nail infection (17%), stomatitis (12%) were more common and hyperglycemia was only 2%. The ADZ9291 study showed that ADZ9291 had better efficacy and was more effective in the T790M mutation group than in the no-mutation group. The ADZ9291 study showed that PFS was better in the T790M mutation group than in the no-mutation group. Another study of Rociletinib yielded similar results. 47 patients with T790M mutations compared with 17 patients without mutations yielded an ORR of 59% vs. 29%, a DCR of 93% vs. 59%, and a median PFS of 13.1 months vs. 5.6 months. was its most common side effect (more than 36%), while side effects such as rash, stomatitis, and nail infection were rare. The Rociletinib study showed that the T790M mutation group had better efficacy than the no mutation group.