Global, multicenter, randomized, phase II trial of gemcitabine and gemcitabine plus AGS-1C4D4 in patients with previously untreated, metastatic pancreatic cancer.
Global, multicenter, randomized, phase II trial of gemcitabine and gemcitabine plus AGS-1C4D4 in patients with previously untreated, metastatic pancreatic cancer.
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DOI：
10.1093/annonc/mdt066
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发表时间：
2013-07
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通讯作者：
B. Wolpin;E. O’Reilly;Yoo-Joung Ko;L. Blaszkowsky;M. Rarick;C. Rocha-Lima;P. Ritch;E. Chan;J. Spratlin;T. Macarulla;E. Mcwhirter;D. Pezet;M. Lichinitser;L. D. Roman;A. Hartford;K. Morrison;L. Jackson;M. Vincent;L. Reyno;Manuel Hidalgo
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作者：
B. Wolpin;E. O’Reilly;Yoo-Joung Ko;L. Blaszkowsky;M. Rarick;C. Rocha-Lima;P. Ritch;E. Chan;J. Spratlin;T. Macarulla;E. Mcwhirter;D. Pezet;M. Lichinitser;L. D. Roman;A. Hartford;K. Morrison;L. Jackson;M. Vincent;L. Reyno;Manuel Hidalgo
我们在一项转移性胰腺癌的随机、II期研究中评估了AGS-1C 4D 4（一种抗前列腺干细胞抗原（PSCA）的全人单克隆抗体）与吉西他滨的疗效。患者和方法美国东部肿瘤协作组（ECOG）体能状态评分为0/1且既往未接受治疗的转移性胰腺癌患者按1：2的比例随机分配至吉西他滨组（1000 mg/m2，每周7次，停药1周，每周3次，每4周1次）或吉西他滨+AGS-1C 4D 4组（48 mg/kg负荷剂量，然后24 mg/kg，每3周1次IV）。主要终点是6个月生存率（SR）。收集存档的肿瘤样品用于通过PSCA表达进行预先计划的分析。结果：2009年4月至2010年5月，196例患者被随机分配至吉西他滨组（n = 63）或吉西他滨+AGS-1C 4D 4组（n = 133）。吉西他滨组和吉西他滨+AGS-1C 4D 4组的6个月SR分别为44.4%（95% CI，31.9-57.5）和60.9%（95% CI，52.1-69.2）（P = 0.03），两组的中位生存期分别为5.5个月和7.6个月，缓解率分别为13.1%和21.6%。在PSCA阳性亚组中，吉西他滨组的6个月SR为57.1%，吉西他滨+AGS-1C 4D 4组为79.5%，在PSCA阴性亚组中为31.6%，吉西他滨+AGS-1C 4D 4组为46.2%。结论：这项随机、II期研究达到了其主要终点，证明在既往未经治疗的转移性胰腺癌患者中，在吉西他滨基础上添加AGS-1C 4D 4可改善6个月SR。ClinicalTrials.gov标识符：NCT 00902291。
BACKGROUND We evaluated AGS-1C4D4, a fully human monoclonal antibody to prostate stem cell antigen (PSCA), with gemcitabine in a randomized, phase II study of metastatic pancreatic cancer. PATIENTS AND METHODS Patients with Eastern Cooperative Oncology Group (ECOG) performance status 0/1 and previously untreated, metastatic pancreatic adenocarcinoma were randomly assigned 1:2 to gemcitabine (1000 mg/m(2) weekly seven times, 1 week rest, weekly three times q4weeks) or gemcitabine plus AGS-1C4D4 (48 mg/kg loading dose, then 24 mg/kg q3weeks IV). The primary end point was 6-month survival rate (SR). Archived tumor samples were collected for pre-planned analyses by PSCA expression. RESULTS Between April 2009 and May 2010, 196 patients were randomly assigned to gemcitabine (n = 63) or gemcitabine plus AGS-1C4D4 (n = 133). The 6-month SR was 44.4% (95% CI, 31.9-57.5) in the gemcitabine arm and 60.9% (95% CI, 52.1-69.2) in the gemcitabine plus AGS-1C4D4 arm (P = 0.03), while the median survival was 5.5 versus 7.6 months and the response rate was 13.1% versus 21.6% in the two arms, respectively. The 6-month SR was 57.1% in the gemcitabine arm versus 79.5% in the gemcitabine plus AGS-1C4D4 arm among the PSCA-positive subgroup and 31.6% versus 46.2% among the PSCA-negative subgroup. CONCLUSIONS This randomized, phase II study achieved its primary end point, demonstrating an improved 6-month SR with addition of AGS-1C4D4 to gemcitabine among patients with previously untreated, metastatic pancreatic adenocarcinoma. ClinicalTrials.gov identifier: NCT00902291.