Piper-Vallillo Andrew J, Sequist Lecia V, Piotrowska Zofia
Department of Medicine, Division of Medical Oncology, Beth Israel Deaconess Medical Center, Boston, MA.
Harvard Medical School, Boston, MA.
J Clin Oncol. 2020 Jun 18:JCO1903123. doi: 10.1200/JCO.19.03123.
Since its approval in April 2018, osimertinib has been widely adopted as first-line therapy for patients with advanced -mutant non -small cell lung cancer (NSCLC). Understanding osimertinib resistance mechanisms and currently available treatment options are essential to selecting optimal second line therapy for patients whose disease progresses during front-line osimertinib. Using data compiled from 6 osimertinib-resistance series, we describe here the heterogeneous profile of EGFR-dependent and independent mechanisms of osimertinib treatment failure. We identified alterations (7%-24%), C797X (0%-29%), SCLC transformation (2%-15%), and oncogene fusions (1%-10%) as the most common mechanisms of resistance. This review provides an evidence-based, algorithmic approach to the evaluation and management of post-osimertinib progression as well as a compendium of active, enrolling clinical trials for this population.
自2018年4月获批以来，奥希替尼已被广泛用作晚期表皮生长因子受体（EGFR）突变非小细胞肺癌（NSCLC）患者的一线治疗药物。了解奥希替尼耐药机制和当前可用的治疗方案对于为一线使用奥希替尼期间疾病进展的患者选择最佳二线治疗至关重要。利用从6个奥希替尼耐药系列收集的数据，我们在此描述了奥希替尼治疗失败的EGFR依赖性和非依赖性机制的异质性特征。我们确定EGFR改变（7%-24%）、C797X（0%-29%）、小细胞肺癌转化（2%-15%）和致癌基因融合（1%-10%）是最常见的耐药机制。本综述提供了一种基于证据的、算法化的方法来评估和管理奥希替尼治疗后的疾病进展，以及针对该人群的正在进行的活性临床试验的概要。
