Crizotinib: an orphan drug for treating non-small-cell lung cancer

Introduction: Crizotinib (PF02341066) was first synthesized as an inhibitor of MET tyrosine kinase (TK) and was later shown to have a potent inhibitory effect on other TKs such as anaplastic lymphoma kinase (ALK) and ROS proto-oncogene 1 (ROS1), which are altered in 3 – 7% and 2% of non-small-cell lung cancers (NSCLCs), respectively. The aim of this review is to discuss the activity of crizotinib in patients with NSCLC whose tumors contain alterations in these genes.Areas covered: PubMed was searched for articles published in English between January 1, 2007, and June 1, 2015 using the terms “lung adenocarcinoma,” “NSCLC,” “crizotinib” and “ALK.” Articles relevant to the topic were also identified from our own files. This article summarizes results from various early-phase and Phase III clinical trials in NSCLC with crizotinib. The mechanisms by which NSCLCs that initially respond to crizotinib eventually acquire resistance to therapy, and the role of newer ALK inhibitors, such as ceritinib, in this setting, has also been briefly discussed.Expert opinion: While crizotinib is currently approved for use and improves outcomes in patients with metastatic ALK-rearranged NSCLC, its role in the management of NSCLCs driven by other alterations (such as MET, ROS1 and NTRK1) and early-stage disease remain to be established by ongoing studies. Furthermore, results from studies directly comparing crizotinib to newer ALK inhibitors are eagerly awaited to help identify the best first-line agent for the management of ALK-rearranged NSCLC.