Integrated Data From 2 Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trials of Active Cellular Immunotherapy With Sipuleucel-T in Advanced Prostate Cancer
Integrated Data From 2 Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trials of Active Cellular Immunotherapy With Sipuleucel-T in Advanced Prostate Cancer
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DOI：
10.1002/cncr.24429
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发表时间：
2009-08-15
期刊：
影响因子：
6.2
通讯作者：
Frohlich, Mark W.
中科院分区：
文献类型：
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作者：
Higano, Celestia S.;Schellhammer, Paul F.;Frohlich, Mark W.
背景：西普鲁切尔-T是ART研究中的主动细胞免疫治疗产品，旨在刺激对前列腺癌的免疫反应。在2个相同设计、随机、双盲、安慰剂对照试验(D9901和D9902A)中，对晚期前列腺癌患者进行了西普鲁塞-T的安全性和有效性评估。方法：在D9901或D9902A中，225例患者被随机分为西普鲁尔-T组(n=147)和安慰剂组(n=78)，每隔大约2周进行3次静脉输注。随机化后，患者被跟踪生存，直到死亡或预先指定的36个月截止期。结果：在D9901和D9902A的综合分析中，随机服用西普鲁尔-T的患者死亡风险降低33%(风险比1.50；95%可信区间1.10-2.05；P=0.011；LOG-RANK)。在对基线预后因素、研究后治疗化疗使用和非前列腺癌相关死亡的失衡进行调整后，治疗效果仍然很强。对西普鲁切尔-T活性的额外支持是由该产品的效力、CDS4上调和总体存活率之间的相关性提供的。与治疗相关的最常见的不良反应是寒战、发热、头痛、虚弱、呼吸困难、呕吐和震颤。这些事件主要是1级和2级，持续时间为1至2天。结论：D9901和D9902A的综合结果显示，与安慰剂相比，接受西普鲁尔-T治疗的患者存活率更高。总体来说，适度的毒性，再加上生存的好处，表明西普鲁尔-T在晚期前列腺癌患者中具有良好的风险-收益比。癌症2009；115：3670-9。(C)2009年美国癌症协会。
BACKGROUND: Sipuleucel-T is art investigational active cellular immunotherapy product designed to stimulate an immune response against prostate cancer. The safety and efficacy of sipuleucel-T was evaluated in 2 identically designed, randomized, double-blind, placebo-controlled trials (D9901 and D9902A) conducted in men with advanced prostate cancer. METHODS: A total of 225 patients were randomized in D9901 or D9902A to sipuleucel-T (n = 147) or placebo (n = 78), given as 3 intravenous infusions approximately 2 weeks apart. Patients were followed for survival until death or a prespecified cutoff of 36 months after randomization. RESULTS: In the integrated analysis of D9901 and D9902A, patients randomized to sipuleucel-T demonstrated a 33% reduction in the risk of death (hazard ratio, 1.50; 95% confidence interval, 1.10-2.05; P = .011; log-rank). The treatment effect remained strong after performing adjustments for imbalances in baseline prognostic factors, poststudy treatment chemotherapy use, and non-prostate cancer-related deaths. Additional support for the activity of sipuleucel-T is provided by the correlation between a measure of the product's potency, CDS4 up-regulation, and overall survival. The most common adverse events associated with treatment were chills, pyrexia, headache, asthenia, dyspnea, vomiting, and tremor. These events were primarily grade 1 and 2, with durations of 1 to 2 days. CONCLUSIONS: The integrated results of D9901 and D9902A demonstrate a survival benefit for patients treated with sipuleucel-T compared with those treated with placebo. The generally modest toxicity profile, coupled with the survival benefit, suggests a favorable risk-benefit ratio for sipuleucel-T in patients with advanced prostate cancer. Cancer 2009;115:3670-9. (C) 2009 American Cancer Society.