{ "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.", "abstract_shown": true, "affiliations": [ "Department of Thoracic Surgery, The Second Hospital of Dalian Medical University, Dalian, China", "China Medical University, Shenyang, China", "Dalian Medical University, Dalian, China" ], "article_type": "Research Article", "arxiv": null, "author_total": 5, "authors": [ { "affs": [ 0 ], "name": "JiaLe Yang" }, { "affs": [ 1 ], "name": "JiaWen Liu" }, { "affs": [ 2 ], "name": "GuanBo Zhao" }, { "name": "HeChen Li" }, { "name": "Ge Sun" } ], "bibtex": "https://research.draconitic.com/paper/5dx061mg165dx.bib", "cited_by": 1, "doi": "10.1371/journal.pone.0358331", "fulltext_url": null, "id": "5dx061mg165dx", "issns": [ "1932-6203" ], "landing_url": "https://doi.org/10.1371/journal.pone.0358331", "language": null, "licence": "CC-BY-4.0", "licence_label": "CC BY 4.0", "licence_source": "journal", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "openalex", "3005|Pharmacovigilance and Adverse Drug Reactions" ], [ "plos", "/Biology and life sciences/Cell biology/Signal transduction/Cell signaling/Membrane receptor signaling/Immune receptor signaling" ], [ "plos", "/Biology and life sciences/Cell biology/Signal transduction/Cell signaling/Neurological signaling" ], [ "plos", "/Biology and life sciences/Neuroscience/Cognitive neuroscience/Cognitive neurology/Cognitive impairment" ], [ "plos", "/Biology and life sciences/Neuroscience/Cognitive science/Cognitive neuroscience/Cognitive neurology/Cognitive impairment" ], [ "plos", "/Engineering and technology/Signal processing" ], [ "plos", "/Medicine and health sciences/Medical conditions/Neurodegenerative diseases/Movement disorders/Ataxia" ], [ "plos", "/Medicine and health sciences/Neurology/Cognitive neurology/Cognitive impairment" ], [ "plos", "/Medicine and health sciences/Neurology/Neurodegenerative diseases/Movement disorders/Ataxia" ], [ "plos", "/Medicine and health sciences/Oncology/Cancers and neoplasms/Lung and intrathoracic tumors/Non-small cell lung cancer" ], [ "plos", "/Medicine and health sciences/Pharmacology/Drug research and development/Drug safety" ], [ "plos", "/Research and analysis methods/Research design/Clinical research design/Adverse events" ] ], "openalex": "W7213307280", "pdf_url": "https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0358331&type=printable", "pmcid": null, "pmid": null, "published": "2026-09-15", "publisher": "Public Library of Science", "ris": "https://research.draconitic.com/paper/5dx061mg165dx.ris", "sources": [ { "first_seen": "2026-10-30T12:17:49Z", "native_id": "10.1371/journal.pone.0358331", "source": "plos", "url": "https://doi.org/10.1371/journal.pone.0358331" } ], "subjects": [ { "field": "biology", "origin": "plos:cell biology", "subfield": "cell-biology" }, { "field": "biology", "origin": "plos:cognitive neuroscience", "subfield": "neuroscience" }, { "field": "medicine", "origin": "plos:neurology", "subfield": "neurology" } ], "title": "Safety profile of entrectinib in NSCLC: Multi-source pharmacovigilance analysis using FAERS and JADER", "title_text": "Safety profile of entrectinib in NSCLC: Multi-source pharmacovigilance analysis using FAERS and JADER", "type": "peer-reviewed", "updated_at": "2026-10-30T12:17:49Z", "url": "https://research.draconitic.com/paper/5dx061mg165dx", "venue": "PLOS One", "versions": [] }