ENGOT-ov-6/TRINOVA-2: Randomised, double-blind, phase 3 study of pegylated liposomal doxorubicin plus trebananib or placebo in women with recurrent partially platinum-sensitive or resistant ovarian cancer

被引：60

作者：

Marth, Christian ^{[1
,2
]}

Vergote, Ignace ^{[3
,4
]}

Scambia, Giovanni ^{[5
,6
]}

Oberaigner, Willi ^{[7
,8
]}

Clamp, Andrew ^{[9
]}

Berger, Regina ^{[1
,2
]}

Kurzeder, Christian ^{[10
,11
]}

Colombo, Nicoletta ^{[12
,13
,14
]}

Vuylsteke, Peter ^{[15
,16
]}

Lorusso, Domenica ^{[17
,18
]}

Hall, Marcia ^{[19
]}

Renard, Vincent ^{[20
,21
]}

Pignata, Sandro ^{[22
,23
]}

Kristeleit, Rebecca ^{[24
]}

Altintas, Sevilay ^{[25
,26
]}

Rustin, Gordon ^{[19
]}

Wenham, Robert M. ^{[27
]}

Mirza, Mansoor Raza ^{[28
,29
]}

Fong, Peter C. ^{[30
]}

Oza, Amit ^{[31
]}

Monk, Bradley J. ^{[32
]}

Ma, Haijun ^{[33
]}

Vogl, Florian D. ^{[33
]}

Bach, Bruce A. ^{[33
]}

机构：

[1] Med Univ Innsbruck, AGO Austria, Innsbruck, Austria

[2] Med Univ Innsbruck, Dept Obstet & Gynecol, Anichstr 35, A-6020 Innsbruck, Austria

[3] Katholieke Univ Leuven, BGOG, Leuven, Belgium

[4] Katholieke Univ Leuven, Dept Obstet & Gynecol, Univ Hosp Leuven, Leuven Canc Inst, Leuven, Belgium

[5] Policlin Univ Agostino Gemelli, MITO, Rome, Italy

[6] Policlin Univ Agostino Gemelli, Dipartimento Tutela Salute Donna & Vita Nascente, Rome, Italy

[7] Tirol Kliniken Ltd, Canc Registry Tyrol, AGO Austria, Innsbruck, Austria

[8] Tirol Kliniken Ltd, Canc Registry Tyrol, Dept Clin Epidemiol, Innsbruck, Austria

[9] Univ Manchester, Christie NHS Fdn Trust, Inst Canc Sci, Dept Med Oncol, Manchester, Lancs, England

[10] Huyssens Stiftung Knappschaft GmbH, AGO Study Grp, Essen, Germany

[11] Huyssens Stiftung Knappschaft GmbH, Dept Gynecol & Gynecol Oncol, Kliniken Essen Mitte Evang, Essen, Germany

[12] MANGO, Milan, Italy

[13] Ist Europeo Oncol, Milan, Italy

[14] Univ Milano Bicocca, Milan, Italy

[15] CHU Univ Catholique Louvain, BGOG, Site St Elisabeth, Namur, Belgium

[16] CHU Univ Catholique Louvain, Dept Med Oncol, Site St Elisabeth, Namur, Belgium

[17] Fdn IRCCS Ist Nazl Tumori, MITO, Milan, Italy

[18] Fdn IRCCS Ist Nazl Tumori, Unita Ginecol Oncol, Milan, Italy

[19] Mt Vernon Canc Ctr, Dept Med Oncol, Northwood, Middx, England

[20] AZ St Lucas, BGOG, Ghent, Belgium

[21] AZ St Lucas, Dept Oncol, Ghent, Belgium

[22] Ist Nazl Tumori Fdn G Pascale IRCCS, MITO, Naples, Italy

[23] Ist Nazl Tumori Fdn G Pascale IRCCS, Dept Urol & Gynecol, Naples, Italy

[24] UCL, Inst Canc, Dept Med Oncol, London, England

[25] Univ Antwerp Hosp, BGOG, Edegem, Belgium

[26] Univ Antwerp Hosp, Dept Med Oncol, Edegem, Belgium

[27] H Lee Moffitt Canc Ctr & Res Inst, Dept Gynecol Oncol, Tampa, FL USA

[28] Rigshosp, NSGO, Copenhagen, Denmark

[29] Rigshosp, Dept Oncol, Copenhagen, Denmark

[30] Auckland City Hosp, Dept Med Oncol, Auckland, New Zealand

[31] Univ Toronto, Princess Margaret Hosp, Dept Med, Toronto, ON M5S 1A1, Canada

[32] Univ Arizona, Ctr Canc, Dign Hlth St Josephs Hosp & Med Ctr, Dept Obstet & Gynecol, Phoenix, AZ USA

[33] Amgen Inc, Global Dev Oncol, Thousand Oaks, CA 91320 USA

来源：

EUROPEAN JOURNAL OF CANCER | 2017年 / 70卷

关键词：

ENGOT-ov-6/TRINOVA-2; Trebananib; Pegylated liposomal doxorubicin; Progression-free survival; Objective response rate; Duration of response; LONG-TERM SURVIVAL; EPITHELIAL OVARIAN; WEEKLY PACLITAXEL; FALLOPIAN-TUBE; TUMOR-GROWTH; REFRACTORY OVARIAN; III TRIAL; AMG; 386; BEVACIZUMAB; CHEMOTHERAPY;

D O I：

10.1016/j.ejca.2016.09.004

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Aims: Trebananib, a peptide-Fc fusion protein, inhibits angiogenesis by inhibiting binding of angiopoietin-1/2 to the receptor tyrosine kinase Tie2. This randomised, double-blind, placebo-controlled phase 3 study evaluated whether trebananib plus pegylated liposomal doxorubicin (PLD) improved progression-free survival (PFS) in patients with recurrent epithelial ovarian cancer. Methods: Women with recurrent ovarian cancer (platinum-free interval <= 12 months) were randomised to intravenous PLD 50 mg/m(2) once every 4 weeks plus weekly intravenous trebananib 15 mg/kg or placebo. PFS was the primary end-point; key secondary end-points were objective response rate (ORR) and duration of response (DOR). Owing to PLD shortages, enrolment was paused for 13 months; the study was subsequently truncated. Results: Two hundred twenty-three patients were enrolled. Median PFS was 7.6 months (95% CI, 7.2-9.0) in the trebananib arm and 7.2 months (95% CI, 4.8-8.2) in the placebo arm, with a hazard ratio of 0.92 (95% CI, 0.68-1.24). However, because the proportional hazards assumption was not fulfilled, the standard Cox model did not provide a reliable estimate of the hazard ratio. ORR in the trebananib arm was 46% versus 21% in the placebo arm (odds ratio, 3.43; 95% CI, 1.78-6.64). Median DOR was improved (trebananib, 7.4 months [95% CI, 5.7-7.6]; placebo, 3.9 months [95% CI, 2.3-6.5]). Adverse events with a greater incidence in the trebananib arm included localised oedema (61% versus 32%), ascites (29% versus 9%) and vomiting (45% versus 33%). Conclusions: Trebananib demonstrated anticancer activity in this phase 3 study, indicated by improved ORR and DOR. Median PFS was not improved. No new safety signals were identified. (C) 2016 Published by Elsevier Ltd.

引用

页码：111 / 121

页数：11

共 38 条

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