{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T12:00:17Z","timestamp":1790251217731,"version":"4.1.0"},"reference-count":34,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2017,2,13]],"date-time":"2017-02-13T00:00:00Z","timestamp":1486944000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010544","name":"Exelixis","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010544","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2017,6]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>Advanced cholangiocarcinoma carries a poor prognosis, and no standard treatment exists beyond first\u2010line gemcitabine\/platinum\u2010based chemotherapy. A single\u2010arm, phase 2 and biomarker study of cabozantinib, a multikinase inhibitor with potent activity against vascular endothelial growth factor receptor 2 (VEGFR2) and MET, was performed for patients with advanced refractory cholangiocarcinoma.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Previously treated patients with unresectable or metastatic cholangiocarcinoma received cabozantinib (60 mg orally and daily on a continuous schedule). The primary endpoint was progression\u2010free survival (PFS). Tumor MET expression and plasma biomarkers were evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      The study enrolled 19 patients with cholangiocarcinoma (female, 68%; median age, 67 years; intrahepatic vs extrahepatic, 84% vs 16%). The median PFS was 1.8 months (95% confidence interval, 1.6\u20105.4 months), and the median overall survival (OS) was 5.2 months (95% confidence interval, 2.7\u201010.5 months). Grade 3\/4 adverse events occurred in 89% of the patients and included neutropenia (5%), hyperbilirubinemia (5%), epistaxis (5%), bowel perforation (5%), enterocutaneous fistulas (5%), and hypertension (11%). One patient with 3\u2009+\u2009MET expression in the tumor stayed on treatment for 278 days, but the MET expression did not correlate with the outcomes in the overall study population. Plasma vascular endothelial growth factor, placental growth factor, and stromal cell\u2013derived factor 1\u03b1 increased and soluble VEGFR2 and angiopoietin 2 decreased after treatment (all\n                      <jats:italic>P<\/jats:italic>\n                      values\u2009&lt;\u2009.01). Plasma tissue inhibitor of matrix metalloproteinase 1 was inversely correlated with PFS, and soluble MET (sMET) and interleukin 6 were inversely correlated with OS.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS<\/jats:title>\n                    <jats:p>\n                      In unselected patients with cholangiocarcinoma, cabozantinib demonstrated limited activity and significant toxicity. In the first clinical trial to assess the role of MET inhibition in cholangiocarcinoma, 1 patient with a MET\u2010high tumor had a prolonged benefit from treatment. Baseline plasma soluble MET was associated with OS. Any further development of this drug in cholangiocarcinoma should include a dose reduction and a biomarker\u2010driven approach.\n                      <jats:bold>\n                        <jats:italic>Cancer<\/jats:italic>\n                        2017;123:1979\u20131988\n                      <\/jats:bold>\n                      . \u00a9\n                      <jats:italic>2017 American Cancer Society<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cncr.30571","type":"journal-article","created":{"date-parts":[[2017,2,13]],"date-time":"2017-02-13T15:36:51Z","timestamp":1487000211000},"page":"1979-1988","source":"Crossref","is-referenced-by-count":105,"title":["A phase 2 and biomarker study of cabozantinib in patients with advanced cholangiocarcinoma"],"prefix":"10.1002","volume":"123","author":[{"given":"Lipika","family":"Goyal","sequence":"first","affiliation":[{"name":"Department of Medicine Massachusetts 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