a Medical Oncology Department , Gustave Roussy , Villejuif , France.
b Early Drug Development Department , Gustave Roussy , Villejuif , France.
Expert Opin Drug Saf. 2018 Dec;17(12):1239-1248. doi: 10.1080/14740338.2018.1549222. Epub 2018 Dec 5.
Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), specifically designed to inhibit EGFR sensitizing and T790M acquired mutations, minimizing exposure in EGFR-wild-type tissues. Areas covered: Osimertinib use in EGFR-mutated non-small cell lung cancer patients is described, focusing on safety and tolerability from studies supporting its approval. Expert opinion: Osimertinib demonstrated greater efficacy, including CNS activity, compared to chemotherapy, with a manageable safety profile in pretreated T790M+ EGFR-mutated patients, leading to FDA approval in 2015 within record time in the oncology field. However, the therapeutic strategy in the EGFR-mutated population is changing, following the FLAURA study in untreated EGFR-mutated patients, in which osimertinib improved progression-free survival compared to other TKIs, with a similar toxicity profile but a lower serious adverse event rate. In April 2018, the FDA and EMA approved osimertinib as first-line therapy for EGFR-mutated patients. Long-term survival data will ultimately establish the true benefit of upfront versus sequential strategies guided by T790M status. These studies favor osimertinib for tolerability and safety, except for the slightly higher rate of interstitial lung disease, but which was nonetheless manageable. In the coming years, osimertinib will be consolidated as standard therapy in the EGFR population and in naïve and pretreated patients, based on mature survival data and the toxicity profile.
奥希替尼是一种第三代表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKI），专门设计用于抑制 EGFR 敏感和 T790M 获得性突变，最大限度地减少 EGFR 野生型组织中的暴露。
本文描述了奥希替尼在 EGFR 突变型非小细胞肺癌患者中的应用，重点介绍了支持其批准的研究中安全性和耐受性。
奥希替尼与化疗相比，在预处理 T790M+ EGFR 突变型患者中具有更高的疗效，包括中枢神经系统活性，且安全性可管理，这促使其在 2015 年在肿瘤学领域创下了批准的记录时间。然而，在 EGFR 突变人群中的治疗策略正在发生变化，这是由于在未经治疗的 EGFR 突变患者中进行的 FLAURA 研究，其中奥希替尼与其他 TKI 相比改善了无进展生存期，具有相似的毒性特征，但严重不良事件发生率较低。2018 年 4 月，FDA 和 EMA 批准奥希替尼作为 EGFR 突变患者的一线治疗药物。长期生存数据最终将确定 T790M 状态指导的 upfront 与序贯策略的真正获益。这些研究除了间质性肺病发生率略高外，奥希替尼在耐受性和安全性方面具有优势，但仍可管理。在未来几年，奥希替尼将基于成熟的生存数据和毒性特征，在 EGFR 人群以及初治和预处理患者中巩固为标准治疗药物。
