Non-small cell lung cancer (NSCLC; 80-85% of all lung cancers) remains the most common cause of cancer-related mortality globally, most often diagnosed in advanced stages. Targeted drugs are currently the most often used therapies for advanced NSCLC patients that harbor molecular alterations, including the echinoderm microtubule-associated protein like 4 (EML4)-anaplastic lymphoma kinase (ALK) translocation. For ALK-positive NSCLC patients, crizotinib, ceritinib, alectinib, and brigatinib, are the first- and second-generation tyrosine kinase inhibitors (TKIs). Although the benefit of them has been demonstrated in series of pivotal clinical trials, most patients who initially derive the benefit latterly develop resistance due to secondary mutations. Lorlatinib, a third-generation inhibitor, is a TKI of ALK and Receptor Tyrosine Kinase C-Ros Oncogene I (ROS-1). It is also a potent TKI that is effectively against known resistant mutants that mediate resistance to first- and second-generation ALK-TKIs. Despite the efficacy and safety data derived from the pivotal phase I/II clinical trial, there are limited data describing the use of lorlatinib and its outcomes in real-world practice settings outside the highly controlled environs of clinical trials. The objective of this study is therefore to evaluate real-world systemic treatment patterns, clinical outcome, therapeutic effect, safety profile of Lorlatinib in advanced NSCLC patients, and also factors associated with clinical outcome in those Lorlatinib treated patients.
