Phase II randomized, double-blind, placebo-controlled study of AMG 386 (trebananib) in combination with cisplatin and capecitabine in patients with metastatic gastro-oesophageal cancer
Phase II randomized, double-blind, placebo-controlled study of AMG 386 (trebananib) in combination with cisplatin and capecitabine in patients with metastatic gastro-oesophageal cancer
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DOI：
10.1093/annonc/mds502
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发表时间：
2013-03-01
影响因子：
50.5
通讯作者：
Bodoky, G.
中科院分区：
文献类型：
--
作者：
Eatock, M. M.;Tebbutt, N. C.;Bodoky, G.
背景：我们评估了AMG 386，一种实验性肽体，可中和血管生成素-1和-2与Tie2受体之间的相互作用，联合顺铂/卡培他滨（CX）作为转移性胃食管癌的一线治疗。患者和方法：转移性胃、胃-食管交界处或食管远端腺癌患者按1:1:1随机分配至CX(顺铂80 mg/m(2) IV Q3W；卡培他滨1000mg /m(2) P.O. BID 14天Q3W)加静脉注射AMG 386 10mg /kg QW （A组）或3mg /kg QW （B组），或安慰剂QW （C组）。主要终点是估计的无进展生存期（PFS）。结果：共有171例患者入组。A组、B组和C组的中位预估PFS分别为4.2、4.9和5.2个月（A+B组联合与C组的风险比为0.98;95% CI 0.67-1.43; P = 0.92）。客观缓解率分别为27% （A组）、43% （B组）和35% （C组）。>= 3级不良事件的发生率在A组为80%，B组为84%，c组为75%。没有药代动力学相互作用的证据。结论：在本研究中，估计AMG 386加CX和安慰剂加CX治疗的PFS和ORR相似。与安慰剂相比，AMG 386加CX的毒性更大，但可控制。先前陈述：本研究的结果之前未在其他地方发表或提交发表。研究结果部分发表于2011年1月20-22日在加州旧金山举行的胃肠癌症研讨会上。
Background: We evaluated AMG 386, an investigational peptibody that neutralizes the interaction between angiopoietins-1 and -2 and the Tie2 receptor, combined with cisplatin/capecitabine (CX) as first-line treatment for metastatic gastro-oesophageal cancer.Patients and Methods: Patients with metastatic gastric, gastro-oesophageal junction, or distal oesophageal adenocarcinoma were randomized 1:1:1 to CX (cisplatin 80 mg/m(2) IV Q3W; capecitabine 1000 mg/m(2) P.O. BID for 14 days Q3W) plus intravenous AMG 386 10 mg/kg QW (Arm A) or 3 mg/kg QW (Arm B), or placebo QW (Arm C). The primary end point was estimated progression-free survival (PFS).Results: A total of 171 patients were enrolled. Median estimated PFS in Arms A, B, and C was 4.2, 4.9, and 5.2 months, respectively (hazard ratio for Arms A+B combined versus Arm C, 0.98; 95% CI 0.67-1.43; P = 0.92). Objective response rates were 27% (Arm A), 43% (Arm B), and 35% (Arm C). Incidence of grade >= 3 adverse events was 80% in Arm A, 84% in Arm B, and 75% in Arm C. There was no evidence of pharmacokinetic interactions.Conclusions: In this study, PFS and ORR were estimated to be similar with AMG 386 plus CX and placebo plus CX treatment. Compared with placebo, toxicity of AMG 386 plus CX was greater but manageable. Previous presentation: The results of this study have not been previously published or submitted for publication elsewhere. The results were presented in part at the Gastrointestinal Cancers Symposium, San Francisco, CA, January 20-22, 2011.