Abstract
Since the discovery of the first-generation ALK inhibitor, many other tyrosine kinase inhibitors have been demonstrated to be effective in the first line or further lines of treatment in patients with advanced non-small cell lung cancer with EMLA4-ALK translocation. This review traces the main milestones in the treatment of ALK-positive metastatic patients and the survival outcomes in the first-line and second-line settings with different ALK inhibitors. It presents the two options available for first-line treatment at the present time: sequencing different ALK inhibitors versus using the most potent inhibitor in front-line treatment. The efficacy outcomes of different ALK inhibitors in the first-line setting; the molecular profile of the disease, including mutation resistances and ALK variants and co-mutations; and patients' co-morbidities and inhibitor toxicities should be taken into account to address the choice of the first-line treatment, as suggested in this review.