{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T12:57:08Z","timestamp":1770814628939,"version":"3.50.1"},"reference-count":19,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2019,3,26]],"date-time":"2019-03-26T00:00:00Z","timestamp":1553558400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004339","name":"Sanofi","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004339","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P50CA127003"],"award-info":[{"award-number":["P50CA127003"]}],"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":["P01CA080124"],"award-info":[{"award-number":["P01CA080124"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2019,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Antiangiogenic therapy is a proven therapeutic modality for refractory gastric and gastroesophageal junction adenocarcinoma. This trial assessed whether the addition of a high affinity angiogenesis inhibitor, ziv\u2010aflibercept, could improve the efficacy of first\u2010line mFOLFOX6 (oxaliplatin, leucovorin, and bolus plus infusional 5\u2010 fluorouracil) in metastatic esophagogastric adenocarcinoma.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients with treatment\u2010naive metastatic esophagogastric adenocarcinoma were randomly assigned (in a 2:1 ratio) in a multicenter, placebo\u2010controlled, double\u2010blind trial to receive first\u2010line mFOLFOX6 with or without ziv\u2010aflibercept (4\u00a0mg\/kg) every 2\u00a0weeks. The primary endpoint was 6\u2010month progression\u2010free survival (PFS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Sixty\u2010four patients were randomized to receive mFOLFOX6 and ziv\u2010aflibercept (43 patients) or mFOLFOX6 and a placebo (21 patients). There was no difference in the PFS, overall survival, or response rate. Patients treated with mFOLFOX6\/ziv\u2010aflibercept tended to be more likely to discontinue study treatment for reasons other than progressive disease (\n                      <jats:italic>P\u00a0<\/jats:italic>\n                      =\u00a0.06). The relative dose intensity of oxaliplatin and 5\u2010fluorouracil was lower in the mFOLFOX6\/ziv\u2010aflibercept arm during the first 12 and 24\u00a0weeks of the trial. There were 2 treatment\u2010related deaths due to cerebral hemorrhage and bowel perforation in the mFOLFOX6\/ziv\u2010aflibercept cohort.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Ziv\u2010aflibercept did not increase the anti\u2010tumor activity of first\u2010line mFOLFOX6 in metastatic esophagogastric cancer, potentially because of decreased dose intensity of FOLFOX. Further evaluation of ziv\u2010aflibercept in unselected, chemotherapy\u2010naive patients with metastatic esophagogastric adenocarcinoma is not warranted.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cncr.32029","type":"journal-article","created":{"date-parts":[[2019,3,26]],"date-time":"2019-03-26T19:24:08Z","timestamp":1553628248000},"page":"2213-2221","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["FOLFOX plus ziv\u2010aflibercept or placebo in first\u2010line metastatic esophagogastric adenocarcinoma: A double\u2010blind, randomized, multicenter phase 2 trial"],"prefix":"10.1002","volume":"125","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7213-3951","authenticated-orcid":false,"given":"James M.","family":"Cleary","sequence":"first","affiliation":[{"name":"Center for Esophageal and Gastric Cancer Dana\u2010Farber\/Brigham and Women\u2019s Cancer Center Boston Massachusetts"},{"name":"Division of Gastrointestinal Cancers, Department of Medical Oncology Dana\u2010Farber Cancer Institute\/Harvard Medical School Boston Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nora K.","family":"Horick","sequence":"additional","affiliation":[{"name":"Biostatistics Center Massachusetts General Hospital Boston Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2377-8301","authenticated-orcid":false,"given":"Nadine Jackson","family":"McCleary","sequence":"additional","affiliation":[{"name":"Center for Esophageal and Gastric Cancer Dana\u2010Farber\/Brigham and Women\u2019s Cancer Center Boston Massachusetts"},{"name":"Division of Gastrointestinal Cancers, Department of Medical Oncology Dana\u2010Farber Cancer Institute\/Harvard Medical School Boston Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas A.","family":"Abrams","sequence":"additional","affiliation":[{"name":"Center for Esophageal and Gastric Cancer Dana\u2010Farber\/Brigham and Women\u2019s Cancer Center Boston Massachusetts"},{"name":"Division of Gastrointestinal Cancers, Department of Medical Oncology Dana\u2010Farber Cancer Institute\/Harvard Medical School Boston Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew B.","family":"Yurgelun","sequence":"additional","affiliation":[{"name":"Center for Esophageal and Gastric Cancer Dana\u2010Farber\/Brigham and Women\u2019s Cancer Center Boston Massachusetts"},{"name":"Division of Gastrointestinal Cancers, Department of Medical Oncology Dana\u2010Farber Cancer Institute\/Harvard Medical School Boston Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher G.","family":"Azzoli","sequence":"additional","affiliation":[{"name":"Steele Laboratories for Tumor Biology Massachusetts General Hospital Cancer 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