A randomised, double-blind, placebo-controlled phase 2 study of trebananib (AMG 386) in combination with FOLFIRI in patients with previously treated metastatic colorectal carcinoma.
A randomised, double-blind, placebo-controlled phase 2 study of trebananib (AMG 386) in combination with FOLFIRI in patients with previously treated metastatic colorectal carcinoma.
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DOI：
10.1038/bjc.2012.594
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发表时间：
2013-02-19
影响因子：
8.8
通讯作者：
Tebbutt, N. C.
中科院分区：
文献类型：
--
作者：
Peeters, M.;Strickland, A. H.;Lichinitser, M.;Suresh, A. V. S.;Manikhas, G.;Shapiro, J.;Rogowski, W.;Huang, X.;Wu, B.;Warner, D.;Jain, R.;Tebbutt, N. C.
这项 2 期研究评估了 trebananib (AMG 386)（一种研究性肽-Fc 融合蛋白，可中和血管生成素-1/2 和 Tie2 受体之间的相互作用）与 FOLFIRI 作为转移性结直肠癌患者的二线治疗。患有结肠或直肠腺癌的患者仅接受一种基于氟嘧啶/奥沙利铂的转移性疾病化疗方案后 6 个月内出现进展。所有患者均接受 FOLFIRI 治疗，并按 2 : 1 随机分组接受每周一次静脉注射 trebananib 10mg kg−1 (QW)（A 组）或安慰剂 QW（B 组）。主要终点是研究者评估的无进展生存期（PFS）。 144 名患者被随机分配（A/B 组，n=95/49）。 A 组和 B 组的中位 PFS 分别为 3.5 和 5.2 个月（风险比 (HR) 1.23；95% CI，0.81-1.86；P=0.33），中位总生存期 (OS) 分别为 11.9 和 8.8 个月（HR 0.90；95% CI；0.53-1.54；P=0.70）。 A 组和 B 组的客观缓解率 (ORR) 分别为 14% 和 0%。治疗组间⩾3级不良事件的发生率相似（A组，61%，B组，65%），包括肺栓塞（1%/4%）、深静脉血栓（5%/2%）和高血压（1%/0%）。与安慰剂加 FOLFIRI 相比，给予 trebananib 加 FOLFIRI 并没有延长 PFS。毒性是可控的，并且与 FOLFIRI 和 trebananib 的已知毒性一致。
This phase 2 study evaluated trebananib (AMG 386), an investigational peptide-Fc fusion protein that neutralises the interaction between angiopoietins-1/2 and the Tie2 receptor, plus FOLFIRI as second-line treatment for patients with metastatic colorectal cancer. Patients had adenocarcinoma of the colon or rectum with progression within 6 months of receiving only one prior fluoropyrimidine/oxaliplatin-based chemotherapy regimen for metastatic disease. All patients received FOLFIRI and were randomised 2 : 1 to also receive intravenous trebananib 10 mg kg−1 once weekly (QW) (Arm A) or placebo QW (Arm B). The primary end point was investigator-assessed progression-free survival (PFS). One hundred and forty-four patients were randomised (Arms A/B, n=95/49). Median PFS in Arms A and B was 3.5 and 5.2 months (hazard ratio (HR) 1.23; 95% CI, 0.81–1.86; P=0.33) and median overall survival (OS) was 11.9 and 8.8 months, respectively (HR 0.90; 95% CI; 0.53–1.54; P=0.70). Objective response rate (ORR) was 14% and 0% in Arms A and B, respectively. Incidence of grade ⩾3 adverse events was similar between treatment arms (Arm A, 61% Arm B, 65%) and included pulmonary embolism (1%/4%), deep vein thrombosis (5%/2%), and hypertension (1%/0%). Administration of trebananib plus FOLFIRI did not prolong PFS compared with placebo plus FOLFIRI. Toxicities were manageable and consistent with those known for FOLFIRI and trebananib.
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血管生成素-1抑制在抑制血管生成和肿瘤生长中的上下文依赖性作用：对AMG 386的影响，AMG 386，一种血管生成蛋白1/2中和肽。
影响因子：
5.7
作者：
Coxon A;Bready J;Min H;Kaufman S;Leal J;Yu D;Lee TA;Sun JR;Estrada J;Bolon B;McCabe J;Wang L;Rex K;Caenepeel S;Hughes P;Cordover D;Kim H;Han SJ;Michaels ML;Hsu E;Shimamoto G;Cattley R;Hurh E;Nguyen L;Wang SX;Ndifor A;Hayward IJ;Falcón BL;McDonald DM;Li L;Boone T;Kendall R;Radinsky R;Oliner JD
通讯作者：
Oliner JD
影响因子：
45.3
作者：
MILANO, G;ETIENNE, MC;DEMARD, F
通讯作者：
DEMARD, F
影响因子：
45.3
作者：
Giantonio, Bruce J.;Catalano, Paul J.;Benson, Al B., III
通讯作者：
Benson, Al B., III
影响因子：
50.5
作者：
Eatock, M. M.;Tebbutt, N. C.;Bodoky, G.
通讯作者：
Bodoky, G.
影响因子：
2.5
作者：
Chung, Yuan-Chang;Hou, Yung-Chi;Hseu, Tzong-Hsiung
通讯作者：
Hseu, Tzong-Hsiung