Department of Haematology-Oncology, National University Cancer Institute of Singapore, National University Health System, 1E Kent Ridge Road, NUHS Tower Block, Level 7, Singapore, 119228, Singapore.
Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
Mol Cancer. 2018 Feb 19;17(1):29. doi: 10.1186/s12943-018-0778-0.
Acquired T790 M mutation is the commonest cause of resistance for advanced non-small cell lung cancer (NSCLC) epidermal growth factor receptor (EGFR) mutant patients who had progressed after first line EGFR TKI (tyrosine kinase inhibitor). Several third generation EGFR TKIs which are EGFR mutant selective and wild-type (WT) sparing were developed to treat these patients with T790 M acquired resistant mutation. Osimertinib is one of the third generation EGFR TKIs and is currently the most advanced in clinical development. Unfortunately, despite good initial response, patients who was treated with third generation EGFR TKI would develop acquired resistance and several mechanisms had been identified and the commonest being C797S mutation at exon 20. Several novel treatment options were being developed for patients who had progressed on third generation EGFR TKI but they are still in the early phase of development. Osimertinib under FLAURA study had been shown to have better progression-free survival over first generation EGFR TKI in the first line setting and likely will become the new standard of care.
获得性 T790M 突变是第一代 EGFR TKI（酪氨酸激酶抑制剂）治疗后进展的晚期非小细胞肺癌（NSCLC）表皮生长因子受体（EGFR）突变患者产生耐药的最常见原因。为了治疗这些具有 T790M 获得性耐药突变的患者，已经开发了几种针对 EGFR 突变选择性和野生型（WT）保留的第三代 EGFR TKI。奥希替尼是第三代 EGFR TKI 之一，目前在临床开发中处于最先进的地位。不幸的是，尽管初始反应良好，但接受第三代 EGFR TKI 治疗的患者会产生获得性耐药，已经确定了几种机制，最常见的是第 20 外显子的 C797S 突变。已经为第三代 EGFR TKI 进展的患者开发了几种新的治疗选择，但它们仍处于早期开发阶段。FLAURA 研究表明，奥希替尼在一线治疗中的无进展生存期优于第一代 EGFR TKI，可能成为新的治疗标准。
