PLoS One. 2026 Sep 15;21(9):e0358331. doi: 10.1371/journal.pone.0358331. eCollection 2026.
ABSTRACT
BACKGROUND: Entrectinib is effective for ROS1-positive non-small cell lung cancer (NSCLC), but its postmarketing safety profile remains incompletely characterized outside clinical trials. We conducted a dual-database pharmacovigilance study to characterize real-world reporting patterns, identify cross-database replicated adverse event signals, explore age- and sex-related reporting heterogeneity, and evaluate time-to-onset patterns.
METHODS: Reports were retrieved from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS; 2020Q1-2025Q4; 520 patients; 1,573 preferred-term [PT] events) and the Japanese Adverse Drug Event Report database (JADER; 2020Q1-2025Q3; 254 patients; 393 PT events). Molecular fusion status was not available for verification. Four disproportionality methods were applied, with reporting odds ratio (ROR) as the primary signal criterion.
RESULTS: At the system organ class level, shared positive signals involved nervous system disorders (FAERS/JADER ROR: 4.48/4.76), cardiac disorders (3.20/5.43), and renal and urinary disorders (2.04/3.92). At the PT level, 23 signals were detected in both databases, whereas 58 PTs were unique to FAERS and 8 to JADER. Representative shared PT signals included dizziness (12.94/14.33), taste disorder (38.03/13.28), renal impairment (6.89/8.18), blood creatinine increased (8.31/24.99), cardiac failure (7.57/8.90), cognitive disorder (18.04/78.29), ataxia (51.73/351.45), syncope (8.87/89.45), myocarditis (3.47/5.91), electrocardiogram QT prolonged (4.01/5.35), and hyperuricaemia (7.36/59.63). Subgroup analyses suggested exploratory age- and sex-related reporting heterogeneity, including relatively more renal and mobility-related reports in older patients and female predominance for ataxia in FAERS. In the FAERS-based time-to-onset analysis, 203 of 520 reports (39.0%) had valid onset data. The median time to onset was 13 days, 70.94% of evaluable reports had onset dates within 30 days, and Weibull analysis suggested an early-failure pattern.
CONCLUSIONS: Entrectinib-associated reports in NSCLC showed reproducible neurologic, cardiac, renal, and laboratory-related disproportional reporting signals across FAERS and JADER. These findings may help prioritize early safety monitoring but should be interpreted as hypothesis-generating signals rather than evidence of incidence or causality.
PMID:42743196 | PMC:PMC13577382 | DOI:10.1371/journal.pone.0358331