{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T12:21:44Z","timestamp":1790857304886,"version":"4.1.0"},"reference-count":34,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[2012,2,1]]},"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p> To estimate the efficacy and toxicity of AMG 386, an investigational peptide-Fc fusion protein that neutralizes the interaction between the Tie2 receptor and angiopoietin-1\/2, plus weekly paclitaxel in patients with recurrent ovarian cancer. <\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and Methods<\/jats:title><jats:p> Patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer were randomly assigned 1:1:1 to receive paclitaxel (80 mg\/m<jats:sup>2<\/jats:sup> once weekly [QW], 3 weeks on\/1 week off) plus intravenous AMG 386 10 mg\/kg QW (arm A), AMG 386 3 mg\/kg QW (arm B), or placebo QW (arm C). The primary end point was progression-free survival (PFS). Secondary end points included overall survival, objective response, CA-125 response, safety, and pharmacokinetics. <\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p> One hundred sixty-one patients were randomly assigned. Median PFS was 7.2 months (95% CI, 5.3 to 8.1 months) in arm A, 5.7 months (95% CI, 4.6 to 8.0 months) in arm B, and 4.6 months (95% CI, 1.9 to 6.7 months) in arm C. The hazard ratio for arms A and B combined versus arm C was 0.76 (95% CI, 0.52 to 1.12; P = .165). Further analyses suggested an exploratory dose-response effect for PFS across arms (Tarone's test, P = .037). Objective response rates for arms A, B, and C were 37%, 19%, and 27%, respectively. The incidence of grade \u2265 3 adverse events (AEs) in arms A, B, and C was 65%, 55%, and 64%, respectively. Frequent AEs included hypertension (8%, 6%, and 5% in arms A, B, and C, respectively), peripheral edema (71%, 51%, and 22% in arms A, B, and C, respectively), and hypokalemia (21%, 15%, and 5% in arms A, B, and C, respectively). AMG 386 exhibited linear pharmacokinetic properties at the tested doses. <\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p> AMG 386 combined with weekly paclitaxel was tolerable, with a manageable and distinct toxicity profile. The data suggest evidence of antitumor activity and a dose-response effect, warranting further studies in ovarian cancer. <\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.2010.34.3178","type":"journal-article","created":{"date-parts":[[2011,12,20]],"date-time":"2011-12-20T04:51:33Z","timestamp":1324356693000},"page":"362-371","source":"Crossref","is-referenced-by-count":173,"title":["Randomized, Double-Blind, Placebo-Controlled Phase II Study of AMG 386 Combined With Weekly Paclitaxel in Patients With Recurrent Ovarian Cancer"],"prefix":"10.1200","volume":"30","author":[{"given":"Beth Y.","family":"Karlan","sequence":"first","affiliation":[{"name":"Author affiliations appear at the end of this article."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit M.","family":"Oza","sequence":"additional","affiliation":[{"name":"Author affiliations appear at the end of this article."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary 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