Open AccessUpdate on Lorlatinib: Role in Reducing the Risk of Disease Progression in ALK-Positive NSCLC
Author(s) -
Karen M Yun,
Lyudmila Bazhenova
Publication year - 2022
Publication title -
cancer management and research
Language(s) - English
Resource type - Journals
ISSN - 1179-1322
DOI - 10.2147/cmar.s283199
Subject(s) - crizotinib , alectinib , ceritinib , alk inhibitor , anaplastic lymphoma kinase , medicine , lung cancer , tyrosine kinase inhibitor , gefitinib , cancer research , oncology , cancer , epidermal growth factor receptor , malignant pleural effusion
Lorlatinib is an oral third-generation inhibitor of anaplastic lymphoma kinase (ALK) with activity in advanced ALK-positive non-small cell lung cancer (NSCLC) in both the first and subsequent line setting. Superior systemic and intracranial efficacy of lorlatinib over crizotinib, a first-generation ALK tyrosine kinase inhibitor (TKI), in treatment-naïve patients with advanced ALK-positive NSCLC was demonstrated by the phase 3 CROWN trial. Lorlatinib retains anti-tumor effect against single and some compound ALK resistance mutations after disease progression on first- and second-generation ALK TKIs. Currently, alectinib, brigatinib, ceritinib, crizotinib and lorlatinib are approved for treatment of advanced ALK-positive NSCLC. However, no head-to-head studies have directly compared lorlatinib to second-generation ALK inhibitors. Herein, we aim to provide an overview of the efficacy and safety of lorlatinib and discuss where lorlatinib stands in the therapeutic approach to advanced ALK-positive NSCLC.