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One of the two major subtypes of lung cancer, non-small cell lung cancer (NSCLC) is a challenging disease to treat, with most patients being diagnosed at a locally advanced or metastatic stage. Despite the use of tumor histology and relevant molecular biomarkers to determine treatment strategies, outcomes remain poor, with a 5-year survival rate of only 24%. In this episode of Oncology Data Advisor, Mark G. Kris, MD, William and Joy Ruane Chair in Thoracic Oncology at Memorial Sloan Kettering Cancer Center, and Nathan Pennell, MD, PhD, Professor of Medicine at the Cleveland Clinic Taussig Cancer Institute, discuss the role of acquired resistance mutations in first-line treatment selection, the potential for central nervous system (CNS) disease, and the efficacy and safety of novel treatment options for patients with ALK-positive advanced NSCLC.