Safety profile of entrectinib in NSCLC: Multi-source pharmacovigilance analysis using FAERS and JADER
- 1Department of Thoracic Surgery, The Second Hospital of Dalian Medical University, Dalian, China
- 2China Medical University, Shenyang, China
- 3Dalian Medical University, Dalian, China
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.
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BibTeX
@article{yang2026safety,
title = {{Safety profile of entrectinib in NSCLC: Multi-source pharmacovigilance analysis using FAERS and JADER}},
author = {JiaLe Yang and JiaWen Liu and GuanBo Zhao and HeChen Li and Ge Sun},
journal = {PLOS One},
year = {2026},
month = sep,
doi = {10.1371/journal.pone.0358331},
url = {https://doi.org/10.1371/journal.pone.0358331},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Safety profile of entrectinib in NSCLC: Multi-source pharmacovigilance analysis using FAERS and JADER
AU - JiaLe Yang
AU - JiaWen Liu
AU - GuanBo Zhao
AU - HeChen Li
AU - Ge Sun
PY - 2026
DA - 2026/09/15
JO - PLOS One
DO - 10.1371/journal.pone.0358331
UR - https://doi.org/10.1371/journal.pone.0358331
AB - 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.
SN - 1932-6203
ER -