{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T05:49:22Z","timestamp":1790660962198,"version":"4.1.0"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2017,2,20]],"date-time":"2017-02-20T00:00:00Z","timestamp":1487548800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Icrucumab (ICR) and ramucirumab (RAM) bind vascular endothelial growth factor (VEGF) receptors 1 and 2 (VEGFR-1 and -2), respectively. This open-label, randomized phase II study evaluated their efficacy and safety in combination with capecitabine (CAP) in patients with previously treated unresectable, locally advanced or metastatic breast cancer.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Patients were randomly assigned (1:1:1) to receive CAP (1,000 mg\/m2 orally twice daily, days 1\u201314) alone or in combination with RAM (10 mg\/kg intravenously [IV], days 1 and 8) (RAM\u2009+\u2009CAP) or ICR (12 mg\/kg IV, days 1 and 8) (ICR\u2009+ CAP) every 21 days. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), tumor response, safety, and pharmacokinetics.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Of 153 patients randomized, 150 received treatment. Median PFS (95% confidence interval) was 22.1 (12.1\u201336.1) weeks on RAM\u2009+\u2009CAP, 7.3 (6.3\u201313.0) weeks on ICR\u2009+\u2009CAP, and 19.0 (12.1\u201324.3) weeks on CAP (hazard ratios [HRs]: 0.691, p\u2009=\u2009.1315, RAM\u2009+\u2009CAP versus CAP; 1.480, p\u2009=\u2009.0851, ICR\u2009+ CAP versus CAP). Median OS was 67.4 weeks on RAM\u2009+\u2009CAP, 62.1 weeks on ICR\u2009+\u2009CAP, and 71.6 weeks on CAP (HRs: 1.833, p\u2009=\u2009.0283, RAM\u2009+\u2009CAP versus CAP; 1.468, p\u2009=\u2009.1550, ICR\u2009+ CAP versus CAP). There was no statistically significant difference in PFS or OS between either combination arm and CAP. Treatment-related adverse events more frequent (by \u226510%) on RAM\u2009+\u2009CAP than on CAP were constipation, decreased appetite, headache, epistaxis, and hypertension. Those more frequent (by \u226510%) on ICR\u2009+\u2009CAP than CAP were anemia, increased lacrimation, periorbital edema, nausea, vomiting, peripheral edema, facial edema, dehydration, and dyspnea.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Combining RAM or ICR with CAP did not improve PFS in the targeted study population.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1634\/theoncologist.2016-0265","type":"journal-article","created":{"date-parts":[[2017,2,21]],"date-time":"2017-02-21T01:40:36Z","timestamp":1487641236000},"page":"245-254","source":"Crossref","is-referenced-by-count":26,"title":["Randomized Phase II Study of Ramucirumab or Icrucumab in Combination with Capecitabine in Patients with Previously Treated Locally Advanced or Metastatic Breast Cancer"],"prefix":"10.1093","volume":"22","author":[{"given":"Linda T.","family":"Vahdat","sequence":"first","affiliation":[{"name":"Weill Cornell Breast Center Weill Cornell Medicine, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Layman","sequence":"additional","affiliation":[{"name":"Ohio State University, Columbus, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise A.","family":"Yardley","sequence":"additional","affiliation":[{"name":"Tennessee Oncology, Nashville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Gradishar","sequence":"additional","affiliation":[{"name":"Northwestern University Feinburg School of Medicine, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamad A.","family":"Salkeni","sequence":"additional","affiliation":[{"name":"Mary Babb Randolph Cancer Center, Robert C. 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USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Sparano","sequence":"additional","affiliation":[{"name":"Weiler Division, Montefiore Medical Center, Bronx, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gladys","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"South Texas Oncology and Hematology, San Antonio, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shande","family":"Tang","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company, Indianapolis, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Gao","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company, Indianapolis, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita P.","family":"Dalal","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company, Indianapolis, Indiana, 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