Journal: The International journal of risk & safety in medicine
This study analyzed post‑marketing safety data to better define the neuropsychiatric adverse event profile of lorlatinib, a third‑generation ALK/ROS1 inhibitor used in ALK‑positive NSCLC, especially for brain metastases.
Using FAERS reports from November 2018 to December 2024 in which lorlatinib was the primary suspect drug, the authors identified 3452 cases and categorized neuropsychiatric adverse events into four domains: cognitive, mood, speech, and psychotic. Disproportionality analyses were performed with Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR).
Key findings:
- Cognitive effects were most frequent, particularly cognitive disorder, memory impairment, and confusional state, all with clear disproportionality signals.
- Mood changes such as affective disorder and personality change were less common but showed strong signal strength.
- Speech disturbances, including slow speech and general speech disorder, also showed marked disproportionality.
- Psychotic symptoms, though rare, had the strongest specificity to lorlatinib, especially olfactory and auditory hallucinations and acute psychosis, with very high ROR/PRR values.
The authors conclude that lorlatinib has a distinctive, multidimensional neuropsychiatric toxicity profile characterized by relatively infrequent but highly specific events. They recommend systematic, proactive monitoring of cognitive function, mood, speech, and psychotic symptoms in patients receiving lorlatinib.