{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T22:49:02Z","timestamp":1788821342481,"version":"build-2803163510"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T00:00:00Z","timestamp":1743379200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Ripretinib has been approved for the treatment of gastrointestinal stromal tumors (GIST). As a novel therapy, several adverse reactions remain unidentified, necessitating a thorough safety evaluation. This study analyzes real-world data from the US Food and Drug Administration Adverse Event Reporting System (FAERS) to investigate adverse events (AEs) associated with ripretinib.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Adverse event reports (AERs) related to ripretinib were extracted from FAERS ASCII data spanning from the second quarter of 2020 to the second quarter of 2024. Following standardization, various disproportionality analyses, including the reporting odds ratio (ROR), proportional reporting ratio (PRR), bayesian confidence propagation neural network (BCPNN), and empirical bayes geometric mean (EBGM), were employed to identify potential safety signals linked to ripretinib. The data provided by medical professionals underwent sensitivity analysis to assess the robustness of the results.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 3,105 ripretinib-related AERs were identified, categorized into 22 system organ classes (SOCs) and 84 preferred terms (PTs). Common AEs, such as alopecia, constipation, and muscle spasms, were consistent with the drug label and clinical trial findings. Notably, the risk of skin cancer associated with ripretinib was further elucidated. Additionally, new signals, including liver abscess and prostatomegaly, were detected. Despite their lower frequency, these signals demonstrated significant strength. A substantial proportion of adverse reactions (n = 322, 39.80%) occurred within the first month of treatment, although a smaller fraction emerged after one year. The sensitivity analysis revealed that most PTs related to skin and subcutaneous tissue maintained high signal values, with 8 cases of skin squamous cell carcinoma-related AEs still reported.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The findings of this study align with established drug guidance and uncover new adverse event signals for ripretinib, thereby enhancing clinical monitoring and facilitating risk identification.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fonc.2025.1542315","type":"journal-article","created":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T04:20:30Z","timestamp":1743394830000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Safety assessment of ripretinib: a real-world adverse event analysis from the food and drug administration adverse event reporting system"],"prefix":"10.3389","volume":"15","author":[{"given":"Sentai","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hewen","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuying","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianfeng","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiwei","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,3,31]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"799","DOI":"10.3324\/haematol.2017.179895","article-title":"The kit and pdgfra switch-control inhibitor dcc-2618 blocks growth and survival of multiple neoplastic cell types in advanced mastocytosis","volume":"103","author":"Schneeweiss","year":"2018","journal-title":"Haematologica"},{"key":"B2","doi-asserted-by":"publisher","first-page":"738","DOI":"10.1016\/j.ccell.2019.04.006","article-title":"Ripretinib (Dcc-2618) is a switch control kinase inhibitor of a broad spectrum of oncogenic and drug-resistant kit and pdgfra variants","volume":"35","author":"Smith","year":"2019","journal-title":"Cancer Cell"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-22-2400","article-title":"Fda approval summary: ripretinib for advanced gastrointestinal stromal tumor","volume":"29","author":"Kumar","year":"2023","journal-title":"Clin Cancer Res"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(20)30168-6","article-title":"Ripretinib in patients with advanced gastrointestinal stromal tumours (Invictus): A double-blind, randomised, placebo-controlled, phase 3 trial","volume":"21","author":"Blay","year":"2020","journal-title":"Lancet Oncol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.esmoop.2022.100520","article-title":"Efficacy and safety of ripretinib in patients with kit-altered metastatic melanoma","volume":"7","author":"Janku","year":"2022","journal-title":"ESMO Open"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-20-0824","article-title":"Ripretinib and mek inhibitors synergize to induce apoptosis in preclinical models of gist and systemic mastocytosis","volume":"20","author":"Gupta","year":"2021","journal-title":"Mol Cancer Ther"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2024.101532","article-title":"Targeting pdgf signaling of cancer-associated fibroblasts blocks feedback activation of hif-1alpha and tumor progression of clear cell ovarian cancer","volume":"5","author":"Mori","year":"2024","journal-title":"Cell Rep Med"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1007\/s12325-023-02576-0","article-title":"Large-scale, multicenter, prospective registry study of ripretinib in advanced gist: A real-world study from China","volume":"40","author":"Zhang","year":"2023","journal-title":"Adv Ther"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.20.00522","article-title":"Switch control inhibition of kit and pdgfra in patients with advanced gastrointestinal stromal tumor: A phase I study of ripretinib","volume":"38","author":"Janku","year":"2020","journal-title":"J Clin Oncol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"295","DOI":"10.3390\/pharmaceutics14020266","article-title":"Using machine learning for pharmacovigilance: A systematic review","volume":"14","author":"Pilipiec","year":"2022","journal-title":"Pharmaceutics"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1002\/pds.1001","article-title":"The reporting odds ratio and its advantages over the proportional reporting ratio","volume":"13","author":"Rothman","year":"2004","journal-title":"Pharmacoepidemiol Drug Saf"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1002\/pds.677","article-title":"Use of proportional reporting ratios (Prrs) for signal generation from spontaneous adverse drug reaction reports","volume":"10","author":"Evans","year":"2001","journal-title":"Pharmacoepidemiol Drug Saf"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1007\/s002280050466","article-title":"A bayesian neural network method for adverse drug reaction signal generation","volume":"54","author":"Bate","year":"1998","journal-title":"Eur J Clin Pharmacol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1002\/pds.1107","article-title":"Comparing data mining methods on the vaers database","volume":"14","author":"Banks","year":"2005","journal-title":"Pharmacoepidemiol Drug Saf"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1002\/sim.1157","article-title":"On the assessment of adverse drug reactions from spontaneous reporting systems: the influence of under-reporting on odds ratios","volume":"21","author":"van der Heijden","year":"2002","journal-title":"Stat Med"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-004-0834-0","article-title":"Postmarketing surveillance of potentially fatal reactions to oncology drugs: potential utility of two signal-detection algorithms","volume":"60","author":"Hauben","year":"2004","journal-title":"Eur J Clin Pharmacol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1186\/s12888-024-05813-0","article-title":"Exploring adverse events of vilazodone: evidence from the faers database","volume":"24","author":"Jiang","year":"2024","journal-title":"BMC Psychiatry"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2023.1320458","article-title":"A real-world pharmacovigilance study of mepolizumab in the fda adverse event reporting system (Faers) database","volume":"14","author":"Zou","year":"2023","journal-title":"Front Pharmacol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1002\/pds.964","article-title":"Comparison of data mining methodologies using Japanese spontaneous reports","volume":"13","author":"Kubota","year":"2004","journal-title":"Pharmacoepidemiol Drug Saf"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.2165\/00002018-200427100-00004","article-title":"Safety related drug-labelling changes: findings from two data mining algorithms","volume":"27","author":"Hauben","year":"2004","journal-title":"Drug Saf"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.2165\/00002018-200629100-00005","article-title":"Comparative performance of two quantitative safety signalling methods: implications for use in a pharmacovigilance department","volume":"29","author":"Almenoff","year":"2006","journal-title":"Drug Saf"},{"key":"B22","doi-asserted-by":"publisher","first-page":"1851","DOI":"10.3390\/cancers15061851","article-title":"Neuropsychiatric adverse drug reactions with tyrosine kinase inhibitors in gastrointestinal stromal tumors: an analysis from the european spontaneous adverse event reporting system","volume":"15","author":"Barbieri","year":"2023","journal-title":"Cancers (Basel)"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.2005.40709.x","article-title":"The epidemiology of Malignant gastrointestinal stromal tumors: an analysis of 1,458 cases from 1992 to 2000","volume":"100","author":"Tran","year":"2005","journal-title":"Am J Gastroenterol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1007\/s00508-014-0589-2","article-title":"Risk factors for the prescription of potentially inappropriate medication (Pim) in the elderly: an analysis of sickness fund routine claims data from Germany","volume":"126","author":"Stock","year":"2014","journal-title":"Wien Klin Wochenschr"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1080\/14737140.2017.1400386","article-title":"New targets and therapies for gastrointestinal stromal tumors","volume":"17","author":"Wozniak","year":"2017","journal-title":"Expert Rev Anticancer Ther"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2007.03.001","article-title":"The role of kit in the management of patients with gastrointestinal stromal tumors","volume":"38","author":"Hornick","year":"2007","journal-title":"Hum Pathol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.2217\/fon-2022-0226","article-title":"Ripretinib in advanced gastrointestinal stromal tumors: an overview of current evidence and drug approval","volume":"18","author":"Goggin","year":"2022","journal-title":"Future Oncol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.22.00294","article-title":"Ripretinib versus sunitinib in patients with advanced gastrointestinal stromal tumor after treatment with imatinib (Intrigue): A randomized, open-label, phase iii trial","volume":"40","author":"Bauer","year":"2022","journal-title":"J Clin Oncol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1007\/s00520-011-1197-6","article-title":"Clinical practice guidelines for the prevention and treatment of egfr inhibitor-associated dermatologic toxicities","volume":"19","author":"Lacouture","year":"2011","journal-title":"Support Care Cancer"},{"key":"B30","article-title":"Long-term sequelae of palmar-plantar erythrodysaesthesia syndrome secondary to 5-fluorouracil therapy","volume":"88","author":"Banfield","year":"1995","journal-title":"J R Soc Med"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2013.11.007","article-title":"Cutaneous manifestations of anti-angiogenic therapy in oncology: review with focus on vegf inhibitors","volume":"90","author":"Ishak","year":"2014","journal-title":"Crit Rev Oncol Hematol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2023.1160117","article-title":"Safety profile of vascular endothelial growth factor receptor tyrosine-kinase inhibitors in pediatrics: A pharmacovigilance disproportionality analysis","volume":"14","author":"Xue","year":"2023","journal-title":"Front Pharmacol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-019-01642-1","article-title":"Reflect-a phase 3 trial comparing efficacy and safety of lenvatinib to sorafenib for the treatment of unresectable hepatocellular carcinoma: an analysis of Japanese subset","volume":"55","author":"Yamashita","year":"2020","journal-title":"J Gastroenterol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.15348","article-title":"Braf inhibitor-associated cutaneous squamous cell carcinoma: new mechanistic insight, emerging evidence for viral involvement and perspectives on clinical management","volume":"177","author":"Wu","year":"2017","journal-title":"Br J Dermatol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.41.1660","article-title":"Atypical melanocytic proliferations and new primary melanomas in patients with advanced melanoma undergoing selective braf inhibition","volume":"30","author":"Zimmer","year":"2012","journal-title":"J Clin Oncol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1007\/s11912-022-01224-0","article-title":"Vegf receptor inhibitor-induced hypertension: emerging mechanisms and clinical implications","volume":"24","author":"Camarda","year":"2022","journal-title":"Curr Oncol Rep"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvz022","article-title":"Vascular cardio-oncology: vascular endothelial growth factor inhibitors and hypertension","volume":"115","author":"Versmissen","year":"2019","journal-title":"Cardiovasc Res"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.33337","article-title":"Increased bleeding risk associated with concurrent vascular endothelial growth factor receptor tyrosine kinase inhibitors and low-molecular-weight heparin","volume":"127","author":"Patel","year":"2021","journal-title":"Cancer"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2025.1542315\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T04:20:46Z","timestamp":1743394846000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2025.1542315\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,31]]},"references-count":38,"alternative-id":["10.3389\/fonc.2025.1542315"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2025.1542315","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,31]]},"article-number":"1542315"}}