{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T02:41:51Z","timestamp":1790649711492,"version":"4.1.0"},"reference-count":22,"publisher":"Wiley","issue":"23","license":[{"start":{"date-parts":[[2017,8,22]],"date-time":"2017-08-22T00:00:00Z","timestamp":1503360000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UM1CA186717"],"award-info":[{"award-number":["UM1CA186717"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NO1\u2010CM\u20102011\u201000,038"],"award-info":[{"award-number":["NO1\u2010CM\u20102011\u201000,038"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30CA33572"],"award-info":[{"award-number":["P30CA33572"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30CA093373"],"award-info":[{"award-number":["P30CA093373"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30CA014089"],"award-info":[{"award-number":["P30CA014089"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30CA014089"],"award-info":[{"award-number":["P30CA014089"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2017,12]]},"abstract":"<jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Targeting the vascular endothelial growth factor (VEGF) pathway has improved outcomes in metastatic renal cell carcinoma (RCC); however, resistance inevitably occurs. CD105 (endoglin) is an angiogenic pathway that is strongly upregulated after VEGF inhibition, potentially contributing to resistance. The authors tested whether TRC105, a monoclonal antibody against endoglin, impacted disease control in patients with previously treated RCC who were receiving bevacizumab.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>Eligible patients with metastatic RCC who had previously received 1 to 4 prior lines of therapy, including VEGF\u2010targeted agents, were randomized 1:1 to receive bevacizumab 10\u2009mg\/kg intravenously every 2 weeks (arm A) or the same plus TRC105 10\u2009mg\/kg intravenously every 2 weeks (arm B). The primary endpoint was progression\u2010free survival (PFS) at 12 and 24 weeks. Correlative studies included serum transforming growth factor \u03b2 (TGF\u03b2) and CD105 levels as well as tissue immunostaining for TGF\u03b2 receptors.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Fifty\u2010nine patients were enrolled (28 on arm A and 31 on arm B), and 1 patient on each arm had a confirmed partial response. The median PFS for bevacizumab alone was 4.6 months compared with 2.8 for bevacizumab plus TRC105 (<jats:italic>P<\/jats:italic>\u2009=\u2009.09). Grade\u2009\u2265\u20093 toxicities occurred in 16 patients (57%) who received bevacizumab compared with 19 (61%) who received bevacizumab plus TRC105 (<jats:italic>P<\/jats:italic>\u2009=\u2009.9). Baseline serum TGF\u03b2 levels below the median (&lt;10.6\u2009ng\/mL) were associated with longer median PFS (5.6 vs 2.1 months; <jats:italic>P<\/jats:italic>\u2009=\u2009.014).<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>TRC105 failed to improve PFS when added to bevacizumab. TGF\u03b2 warrants further study as a biomarker in RCC. <jats:bold><jats:italic>Cancer<\/jats:italic> 2017;123:4566\u20104573<\/jats:bold>. \u00a9 <jats:italic>2017 American Cancer Society<\/jats:italic>.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.30942","type":"journal-article","created":{"date-parts":[[2017,8,22]],"date-time":"2017-08-22T10:25:01Z","timestamp":1503397501000},"page":"4566-4573","source":"Crossref","is-referenced-by-count":41,"title":["Bevacizumab alone or in combination with TRC105 for patients with refractory metastatic renal cell cancer"],"prefix":"10.1002","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5990-298X","authenticated-orcid":false,"given":"Tanya B.","family":"Dorff","sequence":"first","affiliation":[{"name":"University of Southern California Keck School of Medicine, Norris Comprehensive Cancer Center Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeff A.","family":"Longmate","sequence":"additional","affiliation":[{"name":"Department of Biostatistics City of Hope Duarte California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumanta K.","family":"Pal","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology and Experimental Therapeutics City of Hope Duarte California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0435-2527","authenticated-orcid":false,"given":"Walter M.","family":"Stadler","sequence":"additional","affiliation":[{"name":"Hematology\/Oncology Section University of Chicago Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayer N.","family":"Fishman","sequence":"additional","affiliation":[{"name":"Department of Genitourinary Oncology H. Lee Moffitt Cancer Center and Research Institute Tampa Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulka N.","family":"Vaishampayan","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology Karmanos Cancer Center Detroit Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amol","family":"Rao","sequence":"additional","affiliation":[{"name":"University of Southern California Keck School of Medicine, Norris Comprehensive Cancer Center Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacek K.","family":"Pinksi","sequence":"additional","affiliation":[{"name":"University of Southern California Keck School of Medicine, Norris Comprehensive Cancer Center Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James S.","family":"Hu","sequence":"additional","affiliation":[{"name":"University of Southern California Keck School of Medicine, Norris Comprehensive Cancer Center Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1411-0417","authenticated-orcid":false,"given":"David I.","family":"Quinn","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology University of Southern California Keck School of Medicine, Norris Comprehensive Cancer Center Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Primo N.","family":"Lara","sequence":"additional","affiliation":[{"name":"University of California Davis Comprehensive Cancer Center Sacramento California"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,8,22]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21332"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa060655"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa065044"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)61039-9"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa021491"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.284.5419.1534"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0050920"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-410X.2006.06006.x"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-07-4478"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-2879-2"},{"key":"e_1_2_8_12_1","first-page":"4221","article-title":"Differential vascular and transcriptional responses to anti\u2010vascular endothelial growth factor antibody in orthotopic human pancreatic cancer xenografts","volume":"9","author":"Bockhorn M","year":"2003","journal-title":"Clin Cancer Res"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.2174\/156720111793663570"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-12-0098"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)61904-7"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.10.8332"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.19.0108"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-14-1143"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2006.09.6198"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clgc.2014.12.012"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(14)70030-0"},{"key":"e_1_2_8_22_1","doi-asserted-by":"crossref","unstructured":"ChoueiriTK MichaelsonMD PosadasEM et al.A phase 1b dose\u2010escalation study of TRC105 (anti\u2010endoglin antibody) in combination with axitinib in patients with metastatic renal cell carcinoma. Abstract 804. Paper presented at: 40th European Society for Medical Oncology (ESMO) Congress; September 25\u201029 2015; Vienna Austria.","DOI":"10.1093\/annonc\/mdw373.32"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1001-117"}],"container-title":["Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcncr.30942","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cncr.30942","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T17:17:54Z","timestamp":1760289474000},"score":1,"resource":{"primary":{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/10.1002\/cncr.30942"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,8,22]]},"references-count":22,"journal-issue":{"issue":"23","published-print":{"date-parts":[[2017,12]]}},"alternative-id":["10.1002\/cncr.30942"],"URL":"https:\/\/doi.org\/10.1002\/cncr.30942","archive":["Portico"],"relation":{},"ISSN":["0008-543X","1097-0142"],"issn-type":[{"value":"0008-543X","type":"print"},{"value":"1097-0142","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,8,22]]}}}