{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T17:49:59Z","timestamp":1792172999530,"version":"4.4.0"},"reference-count":33,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100031585","name":"Takeda Development Center Americas","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100031585","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Fruquintinib is a highly selective, oral inhibitor of all three vascular endothelial growth factor receptors (\u20101, \u20102, and \u20103) that was approved, including in China, the United States, and the European Union, for the treatment of previously treated metastatic colorectal cancer (mCRC). The efficacy of fruquintinib for mCRC has been consistently demonstrated in randomized, double\u2010blind, Phase 3 clinical studies, including FRESCO (NCT02314819), which enrolled patients in China, and FRESCO\u20102 (NCT04322539), which enrolled patients across 14 countries in North America, Europe, Asia, and Australia. In both studies, patients were randomized 2:1 to receive oral fruquintinib 5\u2009mg or a matching placebo once daily, 3\u2009weeks on, 1\u2009week off, in 28\u2010day\u2009cycles, plus best supportive care, until progression or unacceptable toxicity. Both FRESCO and FRESCO\u20102 met their primary endpoints, demonstrating significant improvements in overall survival (OS) with fruquintinib versus placebo: in FRESCO (fruquintinib:\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009278; placebo:\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009138), median OS was 9.3 with fruquintinib versus 6.6\u2009months with placebo (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.51\u20130.83;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001); in FRESCO\u20102 (fruquintinib:\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009461; placebo:\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009230), median OS was 7.4 with fruquintinib versus 4.8\u2009months with placebo (HR, 0.66; 95% CI, 0.55\u20130.80;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). The most common any\u2010grade treatment\u2010emergent adverse events with fruquintinib (incidence \u2265\u200920% in either study, excluding laboratory abnormalities) were hypertension, palmar\u2010plantar erythrodysesthesia, proteinuria, dysphonia, diarrhea, asthenia, decreased appetite, hypothyroidism, and fatigue. This mini\u2010review summarizes the mechanism of action, pharmacokinetics, key clinical trials, and clinical efficacy and safety data for fruquintinib.\n                  <\/jats:p>","DOI":"10.1111\/cts.70713","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T13:10:53Z","timestamp":1789996253000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Fruquintinib: Mechanism of Action, Clinical, and Translational Science"],"prefix":"10.1111","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0319-1327","authenticated-orcid":false,"given":"Xiaofei","family":"Zhou","sequence":"first","affiliation":[{"name":"Quantitative Clinical Pharmacology, Takeda Development Center Americas, Inc. (TDCA)  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5271-9744","authenticated-orcid":false,"given":"Arvind","family":"Dasari","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Medical Oncology The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0099-874X","authenticated-orcid":false,"given":"Jin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Oncology China Pharmaceutical University Shanghai GoBroad Cancer Hospital  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7054-9536","authenticated-orcid":false,"given":"Caly","family":"Chien","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology, HUTCHMED International Corporation  Florham Park New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0291-1840","authenticated-orcid":false,"given":"Qi","family":"Dong","sequence":"additional","affiliation":[{"name":"Oncology Clinical Science, Takeda Development Center Americas, Inc. (TDCA)  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-7110-9117","authenticated-orcid":false,"given":"Lucy","family":"Chen","sequence":"additional","affiliation":[{"name":"Oncology Clinical Science, Takeda Development Center Americas, Inc. (TDCA)  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixian","family":"Dong","sequence":"additional","affiliation":[{"name":"Patient Safety and Pharmacovigilance, Takeda Development Center Americas, Inc. (TDCA)  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5500-5218","authenticated-orcid":false,"given":"Neeraj","family":"Gupta","sequence":"additional","affiliation":[{"name":"Quantitative Clinical Pharmacology, Takeda Development Center Americas, Inc. (TDCA)  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.4161\/15384047.2014.964087"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2026.03.005"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2018.7855"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)00772-9"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2024.117585"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-16-2157"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12325-019-01013-5"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-016-3069-8"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10637-023-01395-y"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-018-0998-z"},{"key":"e_1_2_12_12_1","unstructured":"U.S. Food & Drug Administration FDA Approves Fruquintinib in Refractory Metastatic Colorectal Cancer(2023) https:\/\/www.fda.gov\/drugs\/resources\u2010information\u2010approved\u2010drugs\/fda\u2010approves\u2010fruquintinib\u2010refractory\u2010metastatic\u2010colorectal\u2010cancer."},{"key":"e_1_2_12_13_1","unstructured":"European Medicines Agency Fruzaqla. European Commission Decision(2024) https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/fruzaqla#overview."},{"key":"e_1_2_12_14_1","unstructured":"SwissMedic Fruzaqla (Active Substance: Fruquintinib). 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