Spectrum of Mechanisms of Resistance to Crizotinib and Lorlatinib in ROS1 Fusion-Positive Lung Cancer.

ABSTRACT:

Purpose

Current standard initial therapy for advanced, ROS proto-oncogene 1, receptor tyrosine kinase fusion (ROS1)-positive (ROS1⁺) non-small cell lung cancer (NSCLC) is crizotinib or entrectinib. Lorlatinib, a next-generation anaplastic lymphoma kinase/ROS1 inhibitor, recently demonstrated efficacy in ROS1⁺ NSCLC, including in crizotinib-pretreated patients. However, mechanisms of lorlatinib resistance in ROS1⁺ disease remain poorly understood. Here, we assessed mechanisms of resistance to crizotinib and lorlatinib.

Experimental design

Biopsies from patients with ROS1 ⁺ NSCLC progressing on crizotinib or lorlatinib were profiled by genetic sequencing.

Results

From 55 patients, 47 post-crizotinib and 32 post-l

SUBMITTER: Lin JJ 

PROVIDER: S-EPMC8127383 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature