{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T15:03:24Z","timestamp":1772118204264,"version":"3.50.1"},"reference-count":22,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2013,10,11]],"date-time":"2013-10-11T00:00:00Z","timestamp":1381449600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2014,2]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>In this randomized phase 2 study, the authors assessed the efficacy and safety of intravenous aflibercept at 2 different doses (2 mg\/kg or 4 mg\/kg) in patients with recurrent, platinum\u2010resistant ovarian, peritoneal, or fallopian tube cancer who developed disease progression after receiving topotecan and\/or pegylated liposomal doxorubicin.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Patients were randomized to receive intravenous aflibercept at a dose of either 2 mg\/kg or 4 mg\/kg every 2 weeks until they developed disease progression or significant toxicity. The primary endpoint was to evaluate Response Evaluation Criteria in Solid Tumor response rates (overall response rate [ORR]\u2009=\u2009complete responses plus partial responses) and to test the null hypothesis (ORR, &gt;5%). Secondary endpoints included time to tumor progression, safety, progression\u2010free survival\/overall survival, drug pharmacokinetics, and immunogenicity. In total, 67 evaluable patients per cohort were planned based on a Simon 2\u2010stage design, and, if those patients responded, then enrollment could extend to 200 patients. Tumor radiographic response was assessed by investigators and by an independent review committee.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>After the first 84 evaluable patients, 8 unconfirmed partial responders were noted (ORR, 10%) across both arms; the Independent Data Monitoring Committee recommended continuing blinded accrual. At study completion, 215 evaluable patients were accrued, including 1 responder of 106 patients (0.9%) in the 2\u2010mg\/kg cohort and 5 responders of 109 patients (4.6%) in the 4\u2010mg\/kg cohort according to the independent review committee. The clinical benefit rate (ORR plus stable disease &gt;6 months) was 12.3% and 11% in the 2\u2010mg\/kg and 4\u2010mg\/kg cohorts, respectively. Treatment\u2010related grade 3 and 4 adverse events included hypertension (25.5% and 27.5% in the 2\u2010mg\/kg and 4\u2010mg\/kg cohorts, respectively), proteinuria (9.4% and 7.3%, respectively), and fatigue (5.7% and 3.7%, respectively). The gastrointestinal perforation rate was low (3 patients; 1.4%).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS<\/jats:title>\n                    <jats:p>\n                      Aflibercept at a dose of either 2 mg\/kg or 4 mg\/kg was generally well tolerated but did not meet the primary endpoint for response.\n                      <jats:bold>\n                        <jats:italic>Cancer<\/jats:italic>\n                        2014;120:335\u2013343\n                      <\/jats:bold>\n                      . \u00a9\n                      <jats:italic>2013 American Cancer Society<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cncr.28406","type":"journal-article","created":{"date-parts":[[2013,10,14]],"date-time":"2013-10-14T07:59:02Z","timestamp":1381737542000},"page":"335-343","source":"Crossref","is-referenced-by-count":40,"title":["Intravenous aflibercept in patients with platinum\u2010resistant, advanced ovarian cancer: Results of a randomized, double\u2010blind, phase 2, parallel\u2010arm study"],"prefix":"10.1002","volume":"120","author":[{"given":"William P.","family":"Tew","sequence":"first","affiliation":[{"name":"Department of Medicine Memorial Sloan\u2010Kettering Cancer Center New York New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicoletta","family":"Colombo","sequence":"additional","affiliation":[{"name":"Gynecologic Oncology, European Institute of Oncology University of Milan\u2010Bicocca Milan 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