{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T01:50:15Z","timestamp":1747187415497,"version":"3.40.5"},"reference-count":24,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2024,7,18]],"date-time":"2024-07-18T00:00:00Z","timestamp":1721260800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005089","name":"Natural Science Foundation of Beijing Municipality","doi-asserted-by":"publisher","award":["L234041"],"award-info":[{"award-number":["L234041"]}],"id":[{"id":"10.13039\/501100005089","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Orthopaedic Surgery"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Multitargeted tyrosine kinase inhibitors (TKIs) have been approved as second\u2010line therapy in refractory sarcoma, prolonging progression\u2010free survival (PFS) but with short\u2010lived duration of disease control. Fruquintinib is a TKI that specifically inhibits vascular endothelial growth factor receptor\u20101,2,3 with no metabolism by liver enzymes. In this retrospective study, we assessed the efficacy and safety of fruquintinib\u2010based treatment in patients with refractory sarcoma after developing several lines of TKI resistance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We retrospectively analyzed the clinical data of patients with refractory sarcoma after they had developed several lines of resistance to TKIs and who received fruquintinib\u2010based treatment from November 2021 to August 2023. The primary endpoint was the progression\u2010free survival rate at 4\u2009months (4m\u2010PFSR). Secondary endpoints were the median PFS, overall survival (OS), objective response rate, disease control rate, and adverse effects (AEs). PFS and OS were estimated using the Kaplan\u2013Meier method. A log\u2010rank test was used to compare survival curves between different clinical and pathological factors. Cox proportional hazards analysis was performed to identify PFS\u2010related prognostic factors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We included 124 patients: 56 (45.2%) with osteosarcoma, 28 (22.6%) with Ewing sarcoma, seven (5.6%) with chondrosarcoma, and 33 (26.6%) with soft tissue sarcomas (STS). Only 18 (14.5%) patients received monotherapy with fruquintinib. With a median follow\u2010up time of 6.8 (interquartile range [IQR], 4.6\u20139.4) months, 22 (17.7%) patients had partial response and 78 (62.9%) had stable disease. The 4m\u2010PFSR was 58.4% (95% confidence interval [CI], 49.6%\u201367.1%). The median PFS and OS were 4.4 (95% CI, 3.9\u20135.0) months and 11.4 (95% CI, 10.3\u201312.5) months. In multivariate analysis, a high hazard ratio for progression was associated with target lesions located outside the lung and bone with 1.79 (95% CI, 1.10\u20132.93; <jats:italic>p<\/jats:italic>\u2009=\u20090.020). Eighty\u2010eight AEs were recorded in 47 (37.9%) patients; the most common were pneumothorax (18\/124, 14.5%), diarrhea (8\/124, 6.5%), oral mucositis (7\/124, 5.6%), and thrombocytopenia (7\/124, 5.6%).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Fruquintinib may be a potential option for patients with refractory sarcoma after developing several lines of TKI resistance, with a satisfactory efficacy and safety profile in combination therapy. However, the degree of contribution of fruquintinib to results is unclear when combined with other effective substances. Additional prospective trials of fruquintinib should be conducted, especially involving different pathological types and combination regimens.<\/jats:p><\/jats:sec>","DOI":"10.1111\/os.14163","type":"journal-article","created":{"date-parts":[[2024,7,19]],"date-time":"2024-07-19T03:04:59Z","timestamp":1721358299000},"page":"2380-2390","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Efficacy and Safety of Fruquintinib\u2010Based Treatment in Patients with Refractory Bone and Soft Tissue Sarcoma after Developing Resistance to Several <scp>TKIs<\/scp>: A Multicenter Retrospective Study"],"prefix":"10.1111","volume":"16","author":[{"given":"Chenchen","family":"Yang","sequence":"first","affiliation":[{"name":"Musculoskeletal Tumor Center Peking University People's Hospital  Beijing 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