Rearrangements involving the ROS1 gene are found in approximately 2% of patients with non-small-cell lung cancer (NSCLC). Based on the results of the pivotal PROFILE 1001 trial, the multikinase tyrosine kinase inhibitor (TKI) crizotinib became the first targeted treatment option for patients with advanced ROS1-positive NSCLC in 2016. Unfortunately, responses to crizotinib tend not to be durable and almost all patients eventually develop disease progression after a certain amount of time, often involving brain metastases. To overcome this crizotinib resistance, several next generation ROS1 inhibitors have been developed and tested in the treatment of crizotinib-pretreated and treatment naïve ROS1-positive advanced NSCLC.
