Combining inhibitors of ALK and ROS1 with other agents for the treatment of non-small cell lung cancer.

AS ALK and ROS1 rearrangements define relatively small subsets of patients with NSCLC. ALK rearrangement is identified in 3% to 5% of patients, whereas ROS1 rearrangement is identified in approximately 1% of patients. Although the percentages are small, the total number of patients diagnosed each year with advanced NSCLC is very large, so small percentages still translate into a sizable number of patients. The clinical features of patients with ALKor ROS1rearranged lung cancers are very similar. Both ALKand ROS1-rearranged patients tend to be younger than average, they usually are never or light smokers, and they almost always have adenocarcinoma histology. Nonetheless, these are distinct subsets of lung cancer patients, and we rarely if ever see overlap of ALK and ROS1 rearrangement. We did recently report a case in which a tumor tested positive for both ALK and ROS1 using fluorescence in situ hybridization assays. However, confirmatory next-generation sequencing demonstrated that the tumor harbored only ALK rearrangement, and not ROS1 rearrangement.1