Trebananib (AMG 386) plus weekly paclitaxel with or without bevacizumab as first-line therapy for HER2-negative locally recurrent or metastatic breast cancer: A phase 2 randomized study

被引:40
|
作者
Dieras, Veronique [1 ]
Wildiers, Hans [2 ]
Jassem, Jacek [3 ]
Dirix, Luc Y. [4 ]
Guastalla, Jean-Paul [5 ]
Bono, Petri [6 ]
Hurvitz, Sara A. [7 ]
Goncalves, Anthony [8 ]
Romieu, Gilles [9 ]
Limentani, Steven A. [10 ]
Jerusalem, Guy [11 ]
Lakshmaiah, K. C. [12 ]
Roche, Henri [13 ]
Sanchez-Rovira, Pedro [14 ]
Pienkowski, Tadeusz [15 ]
Segui Palmer, Miguel Angel [16 ]
Li, Ai [17 ]
Sun, Yu-Nien [17 ]
Pickett, Cheryl A. [17 ]
Slamon, Dennis J. [7 ]
机构
[1] Inst Curie, F-75005 Paris, France
[2] Univ Hosp Leuven, Leuven, Belgium
[3] Med Univ Gdansk, Gdansk, Poland
[4] Gen Hosp Sint Augustinus, Antwerp, Belgium
[5] Ctr Leon Berard, Lyon, France
[6] Univ Helsinki, Cent Hosp, Helsinki, Finland
[7] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA
[8] Inst Paoli Calmettes, Marseilles, France
[9] CRLC Val DAurelle, Montpellier, France
[10] Levine Canc Inst, Charlotte, NC USA
[11] CHU Sart Tilman, B-4000 Liege, Belgium
[12] Kidwai Mem Inst Oncol, Bangalore, Karnataka, India
[13] Inst Claudius Regaud, Toulouse, France
[14] Complejo Hosp Jaen, Jaen, Spain
[15] European Hlth Ctr Otwock, Warsaw, Poland
[16] Corp Sanit Parc Taul, Sabadell, Spain
[17] Amgen Inc, Thousand Oaks, CA 91320 USA
来源
BREAST | 2015年 / 24卷 / 03期
关键词
AMG; 386; trebananib; bevacizumab; paclitaxel; HER2-negative; ADVANCED SOLID TUMORS; DOUBLE-BLIND; OVARIAN-CANCER; GROWTH; ANGIOGENESIS; COMBINATION; TRIAL; VEGF; CHEMOTHERAPY; SUPPRESSION;
D O I
10.1016/j.breast.2014.11.003
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Introduction: This phase 2 randomized study evaluated trebananib (AMG 386), a peptide-Fc fusion protein that inhibits angiogenesis by neutralizing the interaction of angiopoietin-1 and -2 with Tie2, in combination with paclitaxel with or without bevacizumab in previously untreated patients with HER2-negative locally recurrent/metastatic breast cancer. Methods: Patients received paclitaxel 90 mg/m(2) once weekly (3-weeks-on/1-week-off) and were randomly assigned 1: 1: 1: 1 to also receive blinded bevacizumab 10 mg/kg once every 2 weeks plus either trebananib 10 mg/kg once weekly (Arm A) or 3 mg/kg once weekly (Arm B), or placebo (Arm C); or open-label trebananib 10 mg/kg once a week (Arm D). Progression-free survival was the primary endpoint. Results: In total, 228 patients were randomized. Median estimated progression-free survival for Arms A, B, C, and D was 11.3, 9.2, 12.2, and 10 months, respectively. Hazard ratios (95% CI) for Arms A, B, and D versus Arm C were 0.98 (0.61-1.59), 1.12 (0.70-1.80), and 1.28 (0.79-2.09), respectively. The objective response rate was 71% in Arm A, 51% in Arm B, 60% in Arm C, and 46% in Arm D. The incidence of grade 3/4/5 adverse events was 71/9/4%, 61/14/5%, 62/16/3%, and 52/4/7% in Arms A/B/C/D. In Arm D, median progression-free survival was 12.8 and 7.4 months for those with high and low trebananib exposure (AUCss >= 8.4 versus < 8.4 mg.h/mL), respectively. Conclusions: There was no apparent prolongation of estimated progression-free survival with the addition of trebananib to paclitaxel and bevacizumab at the doses tested. Toxicity was manageable. Exposure-response analyses support evaluation of combinations incorporating trebananib at doses > 10 mg/kg in this setting.(C) 2015 Published by Elsevier Ltd.
引用
收藏
页码:182 / 190
页数:9
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