[Central nervous system disorders on lorlatinib: How to detect and manage in practice?]
Vincent Fallet1, Pascal Rouby2, Guido Ahle3
1Tenon Hospital, Department of Pneumology and Thoracic Oncology, Assistance Publique Hôpitaux de Paris and GRC 4, Theranoscan, Sorbonne Université, 75020 Paris, France.
Abstract:
The therapeutic arsenal for advanced ALK positive non-small cell lung cancer has been enriched by specific treatments targeting this molecular abnormality, with five molecules available, including lorlatinib, approved since July 2020. This treatment can have side effects common to other tyrosine kinase inhibitors, as well as other less common disorders affecting the central nervous system such as impaired cognitive function, speech or mood. The prevalence of neuro-psychiatric effects under treatment with lorlatinib reported in studies is nearly 40 % with a mild to moderate intensity in most cases. Given the potential impact on patients' quality of life and even on compliance with treatment, it is essential to include their detection during consultations. The main problem is still to have simple screening tools adapted to clinical practice. A multidisciplinary expert panel (pulmonologist, medical oncologist, psychiatrist, neurologist, pharmacist, nurse) therefore met to propose, based on data from the literature and their clinical experience, elements of management in order to detect these cognitive disorders at an early stage and optimize treatment tolerance. The subjects discussed concern screening and assessment tools, the management of side effects, and their prevention. The use of the practical elements proposed by the group could help optimize the identification and management of central nervous system disorders occurring on lorlatinib.
Insights
Lorlatinib effectively treats advanced ALK-positive non-small cell lung cancer but can cause neuro-psychiatric side effects in nearly 40% of patients. Early detection and management strategies are crucial for optimizing treatment tolerance and patient quality of life.
Area of Science:
- Oncology
- Pharmacology
- Neurology
Background:
- Advanced ALK-positive non-small cell lung cancer (NSCLC) treatment has advanced with targeted therapies like lorlatinib.
- Lorlatinib, approved in July 2020, is a tyrosine kinase inhibitor (TKI) for ALK-positive NSCLC.
- TKIs, including lorlatinib, can cause central nervous system (CNS) side effects, impacting cognitive function, speech, and mood.
Purpose of the Study:
- To address the challenge of detecting and managing neuro-psychiatric side effects associated with lorlatinib treatment in ALK-positive NSCLC.
- To propose practical screening and management strategies for CNS side effects to improve patient quality of life and treatment adherence.
- To provide guidance for clinicians based on literature and expert clinical experience.
Main Methods:
- A multidisciplinary expert panel convened to discuss lorlatinib-induced CNS side effects.
- The panel comprised pulmonologists, medical oncologists, psychiatrists, neurologists, pharmacists, and nurses.
- Discussions focused on literature review and clinical experience to develop management elements.
Main Results:
- Neuro-psychiatric effects occur in nearly 40% of patients treated with lorlatinib, mostly mild to moderate.
- Existing screening tools may not be adequately adapted for routine clinical practice.
- The expert panel aimed to establish practical management elements for early detection and optimization of treatment tolerance.
Conclusions:
- Early detection of CNS disorders during lorlatinib therapy is essential for patient well-being.
- Implementing proposed screening and management strategies can help optimize patient care.
- Multidisciplinary collaboration is key to effectively managing lorlatinib-related neuro-psychiatric side effects in ALK-positive NSCLC.
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