Randomized, Double-Blind, Phase III Trial of Ipilimumab Versus Placebo in Asymptomatic or Minimally Symptomatic Patients With Metastatic Chemotherapy-Naive Castration-Resistant Prostate Cancer
Randomized, Double-Blind, Phase III Trial of Ipilimumab Versus Placebo in Asymptomatic or Minimally Symptomatic Patients With Metastatic Chemotherapy-Naive Castration-Resistant Prostate Cancer
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DOI：
10.1200/jco.2016.69.1584
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发表时间：
2017-01-01
影响因子：
45.3
通讯作者：
Gerritsen, Winald
中科院分区：
文献类型：
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作者：
Beer, Tomasz M.;Kwon, Eugene D.;Gerritsen, Winald
目的：伊匹单抗通过与细胞毒性T淋巴细胞抗原4结合来增强抗肿瘤T细胞反应。我们评估了伊匹单抗对无症状或无症状的前列腺癌患者的治疗效果。患者和方法在这项多中心、双盲、III期试验中，患者被随机分配(2：1)，每3周服用伊匹单抗10 mg/kg或安慰剂，共4次。对于无进展的患者，每3个月给予伊普利玛单抗10 mg/kg或安慰剂维持治疗。结果400名患者被随机分配到ipilimumab组，202名患者接受安慰剂治疗；399名患者接受ipilimumab治疗，199名患者接受安慰剂治疗。Ipilimumab组的中位OS为28.7个月(95%CI，24.5至32.5个月)，而安慰剂组为29.7个月(95%CI，26.1至34.2个月)(风险比，1.11；95.87%CI，0.88至1.39；P=.3667)。Ipilimumab组的中位无进展生存期为5.6个月，安慰剂组为3.8个月(风险比，0.67；95.87%CI，0.55至0.81)。探索性分析显示，使用ipilimumab的前列腺特异性抗原反应率(23%)高于使用安慰剂(8%)。在接受ipilimumab治疗的患者中，腹泻(15%)是唯一报告的与治疗相关的3-4级不良事件(AE)。Ipilimumab组有9人(2%)死于与治疗相关的不良反应；安慰剂组没有死亡。免疫相关的3~4级不良反应发生率分别为31%和2%。结论伊匹单抗不能改善转移性去势抵抗前列腺癌患者的OS。观察到的无进展存活率和前列腺特异性抗原反应率的增加表明患者亚群具有抗肿瘤活性。(C)2016年度美国临床肿瘤学会
PurposeIpilimumab increases antitumor T-cell responses by binding to cytotoxic T-lymphocyte antigen 4. We evaluated treatment with ipilimumab in asymptomatic or minimally symptomatic patients with chemotherapy-naive metastatic castration-resistant prostate cancer without visceral metastases.Patients and MethodsIn this multicenter, double-blind, phase III trial, patients were randomly assigned (2: 1) to ipilimumab 10 mg/kg or placebo every 3 weeks for up to four doses. Ipilimumab 10 mg/kg or placebo maintenance therapy was administered to nonprogressing patients every 3 months. The primary end point was overall survival (OS).ResultsFour hundred patients were randomly assigned to ipilimumab and 202 to placebo; 399 were treated with ipilimumab and 199 with placebo. Median OS was 28.7 months (95% CI, 24.5 to 32.5 months) in the ipilimumab arm versus 29.7 months (95% CI, 26.1 to 34.2 months) in the placebo arm (hazard ratio, 1.11; 95.87% CI, 0.88 to 1.39; P = .3667). Median progression-free survival was 5.6 months in the ipilimumab arm versus 3.8 with placebo arm (hazard ratio, 0.67; 95.87% CI, 0.55 to 0.81). Exploratory analyses showed a higher prostate-specific antigen response rate with ipilimumab (23%) than with placebo (8%). Diarrhea (15%) was the only grade 3 to 4 treatment-related adverse event (AE) reported in >= 10% of ipilimumab-treated patients. Nine (2%) deaths occurred in the ipilimumab arm due to treatment-related AEs; no deaths occurred in the placebo arm. Immune-related grade 3 to 4 AEs occurred in 31% and 2% of patients, respectively.ConclusionIpilimumab did not improve OS in patients with metastatic castration-resistant prostate cancer. The observed increases in progression-free survival and prostate-specific antigen response rates suggest antitumor activity in a patient subset. (C) 2016 by American Society of Clinical Oncology