Proposal for Handling Central Nervous System Symptoms Caused by Lorlatinib

Abstract

Objectives. Lorlatinib is an anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor indicated for the treatment of unresectable advanced or recurrent ALK fusion gene-positive non-small cell lung cancer, as demonstrated by its high efficacy in a global, randomized, phase III trial. The characteristic adverse drug reactions of lorlatinib include central nervous system (CNS) symptoms, such as cognitive impairment, language impairment, mood disorders, and hallucinations, which may require dose interruption or dose reduction depending on the severity of the symptoms. Therefore, pulmonologists and oncologists should exercise caution when diagnosing and treating CNS symptoms. We discussed the management policy for CNS symptoms caused by lorlatinib. Methods. Based on the psychiatrist's review of the diagnosis and grading for patients with lorlatinib-induced CNS symptoms, pulmonologists and the psychiatrist discussed the policy for the management of CNS symptoms. Results. Considering the feasibility of diagnosing and managing lorlatinib-induced CNS symptoms, and the impact of symptoms on the patient's daily life, a flow chart was developed. Conclusions. Regarding the management of CNS symptoms caused by lorlatinib, we propose an approach that basically involves dose interruption or dose reduction and referral to a psychiatrist if the impact on the patient's daily life is significant.