Pirker Robert
Department of Medicine I, Medical University of Vienna, Vienna, Austria.
Curr Opin Oncol. 2016 Mar;28(2):115-21. doi: 10.1097/CCO.0000000000000260.
Patients with epidermal growth factor receptor (EGFR) mutation-positive nonsmall cell lung cancer (NSCLC) develop resistance during therapy with EGFR tyrosine kinase inhibitors (TKIs). In about half of the patients, this resistance is because of the emergence of the T790M mutation. Third-generation TKIs are active against EGFR-activating mutations and the T790M resistance mutation and have only limited efficacy against wild-type EGFR. Here we review the current status of the clinical development of these novel TKIs.
Third-generation TKIs in clinical development include osimertinib, rociletinib, and HM61713. Osimertinib and rociletinib have shown clinical efficacy in phase I/II trials in patients who had acquired resistance to first- or second-generation TKIs. Both TKIs are currently further evaluated in phase III trials as first-line or second-line therapy in patients with advanced EGFR mutation-positive NSCLC. HM61713 is in early clinical development.
Third-generation EGFR TKIs have shown activity in patients with acquired resistance to first- and second-generation EGFR TKIs and may further improve clinical outcome in patients with advanced EGFR mutation-positive NSCLC.
表皮生长因子受体（EGFR）突变阳性的非小细胞肺癌（NSCLC）患者在接受EGFR酪氨酸激酶抑制剂（TKIs）治疗期间会产生耐药性。在大约一半的患者中，这种耐药性是由于T790M突变的出现。第三代TKIs对EGFR激活突变和T790M耐药突变具有活性，而对野生型EGFR的疗效有限。在此，我们综述这些新型TKIs临床开发的现状。
正在进行临床开发的第三代TKIs包括奥希替尼、罗西替尼和HM61713。奥希替尼和罗西替尼在对第一代或第二代TKIs产生耐药性的患者的I/II期试验中已显示出临床疗效。目前，这两种TKIs都在III期试验中作为晚期EGFR突变阳性NSCLC患者的一线或二线治疗进行进一步评估。HM61713正处于早期临床开发阶段。
第三代EGFR TKIs已在对第一代和第二代EGFR TKIs产生耐药性的患者中显示出活性，并可能进一步改善晚期EGFR突变阳性NSCLC患者的临床结局。
