Neurotoxicity associated with ALK inhibitors in the treatment of non-small cell lung cancer: an analysis of the FAERS database

Background ALK inhibitors (ALKis) have substantially improved outcomes in ALK-positive non-small cell lung cancer (NSCLC). Neurological adverse events (AEs) remain clinically relevant, but their reporting patterns and reported time-to-onset (TTO) characteristics in routine pharmacovigilance require further characterization. Methods Neurological AE reports recorded with five ALK inhibitors (crizotinib, ceritinib, alectinib, brigatinib, and lorlatinib) were extracted from FAERS (Q1 2004–Q1 2025). Reporting disproportionality was evaluated at the preferred-term (PT) level using the reporting odds ratio (ROR), proportional reporting ratio (PRR), and Bayesian confidence propagation neural network (BCPNN). TTO analyses were restricted to reports with evaluable timing information, and exploratory subgroup analyses characterized reporting-signal patterns by age, sex, and reporter type. Results The final analysis included 1,473 report-level reports and 2,274 PT-level neurological AE records; one report could contain more than one PT. Lorlatinib, ceritinib, brigatinib, crizotinib, and alectinib had 29, 15, 12, 9, and 9 PTs, respectively, that met all three disproportionality criteria. Among the 1,473 reports, 577 (39.17%) had evaluable TTO information. Recorded onset times among these evaluable reports were more concentrated in the earlier period after treatment initiation, but this distribution does not estimate incidence, absolute risk, or hazard among all exposed patients. Conclusion This pharmacovigilance analysis identifies drug-specific patterns of reported neurological AEs and reported TTO among ALK inhibitors. The findings support clinical awareness and hypothesis generation, but they do not establish causality or comparative clinical safety and should be evaluated in studies with exposure denominators and control of confounding.