%0 Journal Article
%T 第三代EGFR-TKIs耐药后药物治疗研究进展
Research Advances in Drug Therapy after Resistance to Third-Generation EGFR-TKIs
%A 肖东京
%A 吴丹
%A 陈莹
%A 朱本玲
%J Advances in Clinical Medicine
%P 204-210
%@ 2161-8720
%D 2025
%I Hans Publishing
%R 10.12677/acm.2025.154920
%X 第三代表皮生长因子受体–酪氨酸激酶抑制剂(EGFR-TKIs)显著改善了局部晚期及转移性非小细胞肺癌(NSCLC)患者的无进展生存期(PFS)及总生存期(OS)，但耐药问题限制了其长期疗效。在三代EGFR-TKs耐药后，根据耐药机制调整靶向药物治疗，包括换用一/二代靶向药物、联合赛沃替尼、特泊替尼等特定靶点药物可使部分NSCLC患者获益。现有研究表明，以化疗为基础的联合治疗，包括联合免疫治疗、靶向治疗及抗血管药物治疗可延长NSCLC患者的PFS，但其不良反应需引起重视。抗体药物偶联物(ADC)、第四代EGFR-TKIs及双特异性抗体等新型抗肿瘤药物在临床试验中显示出潜在疗效，为三代EGFR-TKIs治疗后进展的NSCLC患者提供了新的选择。未来研究应进一步探索其耐药机制，同时优化药物联合治疗策略，为NSCLC患者的后线治疗提供有效、安全的治疗方案。
The third-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have significantly improved progression-free survival (PFS) and overall survival (OS) in patients with locally advanced and metastatic non-small cell lung cancer (NSCLC). However, the emergence of drug resistance limits their long-term efficacy. Following resistance to third-generation EGFR-TKIs, adjusting targeted therapy based on resistance mechanisms—such as switching to first- or second-generation targeted agents, or combining with specific targeted drugs like savolitinib or tepotinib—can benefit some NSCLC patients. Current research indicates that chemotherapy-based combination therapies, including immunotherapy, targeted therapy, and anti-angiogenic agents, can extend PFS in NSCLC patients, though their adverse effects warrant careful attention. Novel anti-tumor agents such as antibody-drug conjugates (ADC), fourth-generation EGFR-TKIs, and bispecific antibodies have demonstrated potential efficacy in clinical trials, offering new options for NSCLC patients who have progressed after third-generation EGFR-TKIs treatment. Future studies should further explore resistance mechanisms and optimize combination therapy strategies to provide effective and safe treatment options for NSCLC patients in later-line settings.
%K 非小细胞肺癌，
%K 表皮生长因子受体–
%K 酪氨酸激酶抑制剂，
%K 耐药，
%K 联合治疗，
%K 临床试验
Non-Small Cell Lung Cancer
%K Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor
%K Drug Resistance
%K Combination Therapy
%K Clinical Trial
%U http://www.hanspub.org/journal/PaperInformation.aspx?PaperID=110668