Re-Evaluating Progression in an Era of Progress: A Review of First- and Second-Line Treatment Options in Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer

The advent of crizotinib, the first small molecule inhibitor against anaplastic lymphoma kinase (ALK), has led to impressive advances in the care of patients with advanced ALK-rearranged non-small cell lung cancer. The development of second-generation ALK inhibitors, starting with the recent U.S. Food and Drug Administration approval of ceritinib, promises to expand the therapeutic landscape for this cohort of patients. With increasing use of molecularly targeted therapy options, it has been observed that disease progression in patients receiving targeted agents has a heterogeneous biology, manifesting as either oligoprogressive or widely progressive disease, which may require development of innovative treatment strategies. This review discusses the first-and second-generation ALK inhibitors approved or in clinical development, as well as the novel challenges and approaches to disease progression in patients on targeted agents.