Crizotinib for ROS1-Mutated Non–Small-Cell Lung Cancer

Rearrangements of the ROS1 gene (encoding ROS1 proto-oncogene receptor tyrosine kinase) occur in 1% of non–small-cell lung cancer (NSCLC) patients and are a primary driver of carcinogenesis. The entire tyrosine kinase domain of ROS1 is fused to 1 of 12 partner proteins, which enables constitutive activation. Crizotinib, an anaplastic lymphoma kinase (ALK) inhibitor, was identified in preclinical and early phase I trials to have activity against ROS1-mutated NSCLC.

Now, investigators have conducted an industry-funded phase I trial involving 50 patients with metastatic ROS1-mutated NSCLC who were treated with crizotinib (250 mg twice daily). ROS1 rearrangements were identified by break-apart fluorescence in situ hybridization assays. Results w…