{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T23:36:03Z","timestamp":1788478563261,"version":"build-2803163510"},"reference-count":30,"publisher":"Wiley","issue":"S3","license":[{"start":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T00:00:00Z","timestamp":1765238400000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82373335"],"award-info":[{"award-number":["82373335"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20231372"],"award-info":[{"award-number":["BK20231372"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Although therapeutic drug monitoring is crucial for the comprehensive management of gastrointestinal stromal tumors (GISTs), the relationship between plasma concentration of ripretinib and its therapeutic efficacy is unknown. This study aimed to explore the relationship between ripretinib plasma trough concentration (R\u2010C\n                      <jats:sub>trough<\/jats:sub>\n                      ) and clinical efficacy and between ripretinib concentration and the incidence of adverse reactions among Chinese patients with advanced GIST.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The authors analyzed patients with GIST treated continuously for \u22651 month with a consistent daily dose ripretinib in a real\u2010life setting. Peripheral venous blood samples were collected 24 h after the previous dose to measure R\u2010C\n                      <jats:sub>trough<\/jats:sub>\n                      and 4 h after the current dose to identify the maximum concentration (R\u2010C\n                      <jats:sub>4<\/jats:sub>\n                      ). The plasma concentrations of ripretinib and its metabolites were quantified using liquid chromatography\u2010tandem mass spectrometry.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Between June 2021 and October 2024, 102 patients receiving ripretinib were evaluated. Ripretinib treatment resulted in higher mean R\u2010C\n                      <jats:sub>trough<\/jats:sub>\n                      values in the nonprogression group than in the progression group (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a0.05). Patients exhibiting an R\u2010C\n                      <jats:sub>trough<\/jats:sub>\n                      above the threshold (R\u2010C\n                      <jats:sub>min<\/jats:sub>\n                      , 475 ng\/mL) demonstrated a significant improvement in median progression\u2010free survival from 12.8 to 22.6 months (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a0.05). A correlation was observed between ripretinib blood concentration and the occurrence of alopecia, fatigue, hand\u2010foot syndrome, and rashes (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a0.05). Moreover, variability in blood\u2013drug concentrations was observed among patients with different KIT genotypes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Ripretinib and its metabolites maintained consistent plasma concentrations in Chinese patients with advanced GIST. Furthermore, a trough ripretinib concentration &gt;475 ng\/mL was associated with extended survival.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cncr.70149","type":"journal-article","created":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T13:53:55Z","timestamp":1765288435000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Monitoring the plasma concentration of ripretinib and its metabolites in Chinese patients with gastrointestinal stromal tumors in a real\u2010life setting"],"prefix":"10.1002","volume":"131","author":[{"given":"Qiang","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of General Surgery The First Affiliated Hospital of Nanjing Medical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengyuan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of General Surgery The First Affiliated Hospital of Nanjing Medical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of General Surgery Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongjian","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of General Surgery Fujian Medical University Union Hospital  Fuzhou Fujian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoran","family":"Qian","sequence":"additional","affiliation":[{"name":"Department of General Surgery Sir Run Run Shaw Hospital School of Medicine Zhejiang University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Surgery Renji Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of General Surgery Chinese PLA General Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Gastric Cancer Surgery Fudan University Shanghai Cancer Center  Shanghai China"},{"name":"Department of Oncology Shanghai Medical College Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linsen","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of General Surgery Yancheng No. 1 People\u2019s Hospital  Yancheng China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luning","family":"Sun","sequence":"additional","affiliation":[{"name":"Research Division of Clinical Pharmacology First Affiliated Hospital of Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongqing","family":"Wang","sequence":"additional","affiliation":[{"name":"Research Division of Clinical Pharmacology First Affiliated Hospital of Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zekuan","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of General Surgery The First Affiliated Hospital of Nanjing Medical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofeng","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Oncology The Affiliated Cancer Hospital of Nanjing Medical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of General Surgery The First Affiliated Hospital of Nanjing Medical University  Nanjing Jiangsu China"},{"name":"Collaborative Innovation Center for Cancer Personalized Medicine School of Public Health Nanjing Medical University  Nanjing China"},{"name":"Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment Jiangsu Collaborative Innovation Center for Cancer Personalized Medical University  Nanjing 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