A user's guide to lorlatinib. (July 2020)

• Record Type: Journal Article
• Authors: Nagasaka, Misako; Ge, Yubin; Sukari, Ammar; Kukreja, Geetika; Ou, Sai-Hong Ignatius
• Is Part Of: Critical reviews in oncology/hematology. Volume 151(2020)
• Publication Date: 2020-07
• Subjects: Anaplastic lymphoma kinase rearrangement -- ALK inhibitor -- Mechanism of action -- Pharmacology -- Toxicity management; Oncology -- Periodicals; Hematology -- Periodicals; 616.994
• DOI: 10.1016/j.critrevonc.2020.102969
• Languages: English
• ISSNs: 1040-8428

Abstract

Graphical abstract: Abstract: Rearrangements of the ALK gene are found in approximately 5% of non-small-cell lung cancer. It is of particular importance to test for this rearrangement in patients with metastatic lung adenocarcinoma because these tumors are highly sensitive to therapy with ALK-targeted inhibitors. Lorlatinib is a reversible potent third generation tyrosine kinase inhibitor that is highly selective and targets ALK and ROS1. It was developed to target resistant ALK mutants including the most common G1202R. Lorlatinib has excellent central nervous system (CNS) penetration and its efficacy has also been demonstrated even in patients with intracranial metastases after progression on second generation ALK inhibitors. Potential toxicities include neurocognitive effects and hyperlipidemia. "A User's Guide to Lorlatinib" reviews the mechanism of action, pharmacology and clinical trial data. Also covering the management of adverse events, this "guide" has been prepared to be a practical reference tool to both clinicians and basic researchers.