Crizotinib in the Treatment of Non–Small-Cell Lung Cancer

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An anaplastic lymphoma kinase (ALK) translocation giving rise to activated ALK tyrosine kinase is present in approximately 5% of non–small-cell lung cancers (NSCLCs). Crizotinib is an oral tyrosine kinase inhibitor targeting ALK, met proto-oncogene, and c-ros oncogene 1 (ROS1). It was recently approved in several countries for the treatment of patients with advanced, ALK-rearranged NSCLC. In 2012, results from the first phase III trial showing superiority of crizotinib compared with standard chemotherapy in second-line treatment of ALK-positive NSCLC were presented. Furthermore, crizotinib was recently shown to be active in ROS1-rearranged NSCLC. Here, we give an overview of the molecular pathogenesis of ALK-rearranged NSCLC, the pharmacokinetic and pharmacodynamic properties of crizotinib, and clinical trials of crizotinib for ALK-rearranged NSCLC.

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