Department of Hematology & Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA.
Future Oncol. 2019 Mar;15(8):805-816. doi: 10.2217/fon-2018-0626. Epub 2019 Jan 18.
Mutations in the EGFR occur in approximately 10-35% of non-small-cell lung cancer (NSCLC) patients. Osimertinib is a third-generation oral small molecule inhibitor of EGFR, active against the common targetable activating EGFR mutations in L858R and exon 19 deletion; it also inhibits the T790M mutation. It was initially developed and approved for the treatment of acquired resistance to EGFR inhibition mediated by the T790M pathway activation. Recently, the FLAURA trial showed significantly improved progression-free survival with osimertinib compared with the first generation EGFR tyrosine kinase inhibitors gefitinib or erlotinib; this has led to its approval by US FDA and European Medicines Agency (EMA) as frontline therapy. Ongoing studies will define the resistance mechanisms to osimertinib, novel combination approaches and role in earlier stages of NSCLC.
EGFR 基因突变约见于 10%-35%的非小细胞肺癌（NSCLC）患者。奥希替尼是一种第三代针对 EGFR 的口服小分子抑制剂，针对 L858R 和外显子 19 缺失这两种常见的可靶向激活 EGFR 突变具有活性；它还能抑制 T790M 突变。奥希替尼最初是为了治疗由 T790M 通路激活介导的对 EGFR 抑制的获得性耐药而研发并获得批准的。最近，FLAURA 试验显示，与第一代 EGFR 酪氨酸激酶抑制剂吉非替尼或厄洛替尼相比，奥希替尼显著改善了无进展生存期；这促使美国食品药品监督管理局（FDA）和欧洲药品管理局（EMA）批准其作为一线治疗药物。正在进行的研究将确定奥希替尼的耐药机制、新型联合治疗方法及其在 NSCLC 早期阶段的作用。
