Targeted therapy with epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKIs) is regarded as the main accepted first-line treatment on EGFR mutation in non-small cell lung cancer (NSCLC). Although targeted therapy for the first and two generation of TKIs may lead to longer progression-free survival (PFS) and better tolerance for patients, the long-term treatment will inevitably lead to drug resistance. Among them, more than 50% of acquired resistance is associated with T790M mutation. The latest guidelines from the National Comprehensive Cancer Network (NCCN) have been proposed that the three generation of TKI (Osimertinib) can be used in first-line TKI therapy progress with detecting T790M mutations in patients. Encouraged by the treatment time of the median PFS up to 13 months and sequential EGFR-TKIs treatment which brought from the three generation of TKI, we also face serious challenges, such as how to achieve the detecting and the dynamic monitoring of T790M, the research progress, mechanism of drug resistance and subsequent treatment of the existing three generation TKI etc. This article will revolve around the above hot issues.
目前，针对表皮生长因子受体（epidermal growth factor receptor, EGFR）突变的非小细胞肺癌（non-small cell lung cancer, NSCLC）公认的一线治疗方案是以EGFR酪氨酸激酶抑制剂（tyrosine kinase inhibitors, TKIs）为主的靶向治疗，尽管一代、二代TKIs带来的靶向治疗可为患者带来更长的无进展生存（progression-free survival, PFS），及更好的耐受，但其远期治疗不可避免会出现耐药。其中，50%以上的获得性耐药与T790M突变有关，因此美国国立综合癌症网络（National Comprehensive Cancer Network, NCCN）推出的最新指南已经提出三代TKI（Osimertinib，奥西替尼）可用于一线TKI治疗进展同时检出T790M突变的患者。但就在三代TKI为我们带来令人鼓舞的可长达13个月的中位PFS及延续着后EGFR-TKIs治疗时代的同时，也面临着严峻的挑战，如怎样实现T790M的检测及动态监测、对已有三代TKI的研究进展、出现三代TKI耐药的机制及后续治疗等，本文将围绕以上各热点问题展开综述。.