ALK (anaplastic lymphoma kinase) rearrangements occur in approximately 3-7% of NSCLCs and are more common in younger patients, never-smokers, and those with adenocarcinoma.
Detection methods include fluorescence in situ hybridization (FISH), immunohistochemistry (IHC), and next-generation sequencing. Each method has advantages; NGS can detect ALK rearrangements alongside other actionable alterations simultaneously.
ALK inhibitors such as crizotinib, ceritinib, alectinib, brigatinib, and lorlatinib have transformed outcomes for ALK-positive patients. Alectinib and lorlatinib are currently preferred first-line options due to superior progression-free survival and central nervous system activity compared to chemotherapy.