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. READ ARTICLE

Critical Reviews in Oncology/Hematology DOI:10.1016/j.critrevonc.2020.102969

Authors: Misako Nagasaka, Yubin Ge, Ammar Sukari, Geetika Kukreja, Sai-Hong IgnatiusOu

EditorialKirk SmithJuly 1, 2020Anaplastic lymphoma kinase rearrangement, ALK inhibitor, Mechanism of action, Pharmacology, Toxicity management

Concomitant EGFR Mutation and EML4-ALK Rearrangement in Lung Adenocarcinoma Is More Frequent in Multifocal Lesions

Background: The coexistence of epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) rearrangement in patients with multifocal lung adenocarcinomas (LUAC) constitutes a rare molecular subtype of lung cancer. We aimed to investigate the intertumoral heterogeneity of pathologic and genetic characteristics of multifocal LUAC with EGFR/ALK co-alterations. Conclusion: The results highlight the importance of distinguishing synchronous primary tumors from intrapulmonary metastases, and of assessing the relative abundance of EGFR mutation and ALK rearrangement in patients with multifocal adenocarcinomas with EGFR/ALK co-alterations. READ ARTICLE

Clinical Lung Cancer DOI:doi.org/10.1016/j.cllc.2019.04.008

Authors: Jun Fan, Xiaofang Dai, Zhenkao Wang, Bo Huang, Heshui Shi, Danju Luo, Jiwei Zhang, Weijing Cai, Xiu Nie, Fred R.Hirsch

Case StudyKirk SmithJuly 1, 2019Anaplastic lymphoma kinase rearrangement, Clonal evolution, Epidermal growth factor receptor, Intertumoral heterogeneity, Multifocal lung adenocarcinomas