Emerging Treatment Paradigms for EGFR-Mutant Lung Cancers Progressing on Osimertinib: A Review

被引：141

作者：

Piper-Vallillo, Andrew J. ^{[1
,2
,3
]}

Sequist, Lecia, V ^{[2
,3
]}

Piotrowska, Zofia ^{[2
,3
]}

机构：

[1] Beth Israel Deaconess Med Ctr, Dept Med, Div Med Oncol, Boston, MA 02215 USA

[2] Harvard Med Sch, Boston, MA 02115 USA

[3] Massachusetts Gen Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02114 USA

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2020年 / 38卷 / 25期

关键词：

TYROSINE KINASE INHIBITORS; ACQUIRED-RESISTANCE; 1ST-LINE ERLOTINIB; BRAIN METASTASES; OPEN-LABEL; MUTATION; THERAPY; COMBINATION; CRIZOTINIB; ADENOCARCINOMA;

D O I：

10.1200/JCO.19.03123

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Since its approval in April 2018, osimertinib has been widely adopted as first-line therapy for patients with advancedEGFR-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 identifiedMETalterations (7%-24%),EGFRC797X (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.

引用

页码：2926 / +

页数：13

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