ROS1-rearranged non-small cell lung cancer: Understanding biology and optimizing management in the era of new approvals

Rearrangements involving the ROS1 gene are infrequent in non-small cell lung cancer (NSCLC) but represent an important targetable driver alteration. Occurring most commonly in patients with adenocarcinoma who have a light or never smoking history, ROS1 rearrangements can be identified by either fluorescence in-situ hybridization (FISH) or next-generation sequencing techniques. Multiple tyrosine kinase inhibitors (TKIs) are now available for the effective treatment of ROS1-rearranged NSCLC in the metastatic setting including crizotinib, entrectinib, and repotrectinib as first-line therapy options. In addition, newer targeted therapies with increased selectivity for ROS1 over other targets are also emerging. As treatment of the disease continues to evolve, understanding the clinical course of patients with ROS1-rearranged NSCLC as well as the data supporting the latest therapy options is key to timely, effective, and longitudinal care.