Randomized, Double-Blind, Placebo-Controlled Phase II Study of AMG 386 Combined With Weekly Paclitaxel in Patients With Recurrent Ovarian Cancer

被引：157

作者：

Karlan, Beth Y. ^{[1
]}

Oza, Amit M. ^{[10
]}

Richardson, Gary E. ^{[15
]}

Provencher, Diane M. ^{[12
]}

Hansen, Vincent L. ^{[5
]}

Buck, Martin ^{[14
]}

Chambers, Setsuko K. ^{[6
]}

Ghatage, Prafull ^{[13
]}

Pippitt, Charles H., Jr. ^{[7
]}

Brown, John V., III ^{[2
]}

Covens, Allan ^{[11
]}

Nagarkar, Raj V. ^{[17
]}

Davy, Margaret ^{[16
]}

Leath, Charles A., III ^{[8
]}

Hoa Nguyen ^{[9
]}

Stepan, Daniel E. ^{[3
]}

Weinreich, David M. ^{[3
]}

Tassoudji, Marjan ^{[4
]}

Sun, Yu-Nien ^{[3
]}

Vergote, Ignace B. ^{[18
]}

机构：

[1] Cedars Sinai Med Ctr, Div Gynecol Oncol, Los Angeles, CA 90048 USA

[2] Gynecol Oncol Associates, Newport Beach, CA USA

[3] Amgen Inc, Thousand Oaks, CA USA

[4] Amgen Inc, San Francisco, CA USA

[5] No Utah Associates, Ogden, UT USA

[6] Univ Arizona, Arizona Canc Ctr, Tucson, AZ USA

[7] Piedmont Hematol Oncol Associates, Winston Salem, NC USA

[8] Brooke Army Med Ctr, Ft Sam Houston, TX 78234 USA

[9] Sheridan Healthcare Corp, Hollywood, FL USA

[10] Princess Margaret Hosp, Toronto, ON, Canada

[11] Toronto Sunnybrook Reg Canc Ctr, Toronto, ON, Canada

[12] Hop Notre Dame De Bon Secours, Ctr Hosp Univ Montreal, Montreal, PQ, Canada

[13] Tom Baker Canc Clin, Calgary, AB, Canada

[14] Sir Charles Gairdner Hosp, Perth, WA 6000, Australia

[15] Cabrini Hosp, Melbourne, Vic, Australia

[16] Royal Adelaide Hosp, Adelaide, SA 5000, Australia

[17] Curie Manavata Canc Ctr, Nasik, Maharashtra, India

[18] Univ Hosp Leuven, Louvain, Belgium

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2012年 / 30卷 / 04期

关键词：

GASTROINTESTINAL PERFORATION; CLINICAL-TRIAL; TUMOR-GROWTH; BEVACIZUMAB; ANGIOGENESIS; CHEMOTHERAPY; CA-125; ANGIOPOIETIN-2; SUPPRESSION; INHIBITION;

D O I：

10.1200/JCO.2010.34.3178

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Purpose 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. Patients and Methods Patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer were randomly assigned 1: 1: 1 to receive paclitaxel (80 mg/m(2) 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. Results 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 >= 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. Conclusion 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. J Clin Oncol 30: 362-371. (C) 2011 by American Society of Clinical Oncology

引用

页码：362 / 371

页数：10

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