A randomized, placebo-controlled phase 2 study of ganitumab (AMG 479) or conatumumab (AMG 655) in combination with gemcitabine in patients with metastatic pancreatic cancer
A randomized, placebo-controlled phase 2 study of ganitumab (AMG 479) or conatumumab (AMG 655) in combination with gemcitabine in patients with metastatic pancreatic cancer
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DOI：
10.1093/annonc/mds142
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发表时间：
2012-11-01
影响因子：
50.5
通讯作者：
Fuchs, C. S.
中科院分区：
文献类型：
--
作者：
Kindler, H. L.;Richards, D. A.;Fuchs, C. S.
在转移性胰腺癌患者的随机2期试验中，我们评估了ganitumab（胰岛素样生长因子1受体的单抗拮抗剂）或conatumumab（人类死亡受体5的单抗拮抗剂）联合吉西他滨的疗效和安全性。先前未治疗的转移性胰腺腺癌和东部肿瘤合作组（ECOG）表现状态< 1的患者随机分为1:1:1组，静脉注射吉西他滨1000mg /m(2)（每个28天周期的第1、8和15天），联合开放标签甘尼单抗（每2周12mg /kg [Q2W]）、双盲科纳单抗（10mg /kg Q2W）或双盲安慰剂Q2W。主要终点为6个月生存率。共有125名患者被随机分组。ganitumab组的6个月生存率为57% (95% CI 41-70)， conatumumab组为59%(42-73)，安慰剂组为50%（33-64）。ganitumab、conatumumab和安慰剂组的>= 3级不良事件分别包括中性粒细胞减少（18/22/13%）、血小板减少（15/17/8%）、疲劳（13/12/5%）、丙氨酸转氨酶升高（15/5/8%）和高血糖（18/2/3%）。甘尼单抗联合吉西他滨具有可耐受的毒性，并显示出改善6个月生存率和总生存率的趋势。有必要对这种组合进行进一步调查。通过6个月生存率评估，Conatumumab联合吉西他滨显示出一些活性证据。
We evaluated the efficacy and safety of ganitumab (a mAb antagonist of insulin-like growth factor 1 receptor) or conatumumab (a mAb agonist of human death receptor 5) combined with gemcitabine in a randomized phase 2 trial in patients with metastatic pancreatic cancer.Patients with a previously untreated metastatic pancreatic adenocarcinoma and an Eastern Cooperative Oncology Group (ECOG) performance status < 1 were randomized 1 : 1 : 1 to i.v. gemcitabine 1000 mg/m(2) (days 1, 8, and 15 of each 28-day cycle) combined with open-label ganitumab (12 mg/kg every 2 weeks [Q2W]), double-blind conatumumab (10 mg/kg Q2W), or double-blind placebo Q2W. The primary end point was 6-month survival rate.In total, 125 patients were randomized. The 6-month survival rates were 57% (95% CI 41-70) in the ganitumab arm, 59% (42-73) in the conatumumab arm, and 50% (33-64) in the placebo arm. The grade >= 3 adverse events in the ganitumab, conatumumab, and placebo arms, respectively, included neutropenia (18/22/13%), thrombocytopenia (15/17/8%), fatigue (13/12/5%), alanine aminotransferase increase (15/5/8%), and hyperglycemia (18/2/3%).Ganitumab combined with gemcitabine had tolerable toxicity and showed trends toward an improved 6-month survival rate and overall survival. Additional investigation into this combination is warranted. Conatumumab combined with gemcitabine showed some evidence of activity as assessed by the 6-month survival rate.