Lorlatinib (Lorbrena), An ALK Inhibitor for Treating NSCLC

Chapter 11 Lorlatinib (Lorbrena), An ALK Inhibitor for Treating NSCLC Ruby M. Aaron, Ruby M. AaronSearch for more papers by this authorHayden K. Low, Hayden K. LowSearch for more papers by this authorBenjamin T. Sokol, Benjamin T. SokolSearch for more papers by this authorAmy B. Dounay, Amy B. DounaySearch for more papers by this author Ruby M. Aaron, Ruby M. AaronSearch for more papers by this authorHayden K. Low, Hayden K. LowSearch for more papers by this authorBenjamin T. Sokol, Benjamin T. SokolSearch for more papers by this authorAmy B. Dounay, Amy B. DounaySearch for more papers by this author Book Editor(s):Jie Jack Li, Jie Jack LiSearch for more papers by this author First published: 22 September 2022 https://doi.org/10.1002/9781119847281.ch11 AboutPDFPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Summary Lung cancer is the leading cause of global cancer mortality. Lung cancer presents in two main forms: non-small cell lung cancer (NSCLC), diagnosed in 84% of cases, and small cell lung cancer. Anaplastic lymphoma kinase (ALK) and c-ROS oncogene 1 rearrangements, presenting in 3–8% and 1–2% of patients, respectively, are two specific genetic variants targeted by new NSCLC therapeutics. For patients treated with first- or second-generation ALK inhibitors, metastases in the central nervous system (CNS) are common, due to an inability of these drugs to achieve therapeutic concentrations in the CNS. Lorlatinib was designed to achieve increased drug exposure in the CNS as well as an improved overall pharmacokinetic profile compared to first- and second-generation ALK inhibitors. Preclinical studies showed that lorlatinib is highly effective in patient-derived and genetically-engineered cancer models driven by drug-resistant ALK. Current Drug Synthesis, 1st Edition RelatedInformation