Overall Survival Analysis of a Phase II Randomized Controlled Trial of a Poxviral-Based PSA-Targeted Immunotherapy in Metastatic Castration-Resistant Prostate Cancer
Overall Survival Analysis of a Phase II Randomized Controlled Trial of a Poxviral-Based PSA-Targeted Immunotherapy in Metastatic Castration-Resistant Prostate Cancer
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DOI：
10.1200/jco.2009.25.0597
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发表时间：
2010-03-01
影响因子：
45.3
通讯作者：
Godfrey, Wayne R.
中科院分区：
文献类型：
--
作者：
Kantoff, Philip W.;Schuetz, Thomas J.;Godfrey, Wayne R.
目的前列腺癌治疗性前列腺特异性抗原(PSA)靶向痘病毒疫苗耐受性良好。在一项随机、对照、双盲的II期研究中，对前列环素-VF治疗的安全性、无进展生存期(PFS)和总生存期(OS)的延长进行了评估。患者和方法总共125名患者在接种系列的多中心试验中随机分配。符合条件的患者患有最小症状的去势抵抗转移性前列腺癌(MCRPC)。Prostvac-VF由两个编码PSA转基因的重组病毒载体和三个免疫共刺激分子(B7.1、ICAM-1和LFA-3)组成。以牛痘为基础的载体被用于启动，随后计划进行六次基于鸡痘的载体增强。患者按2：1的比例接受Prostvac-VF加粒细胞-巨噬细胞集落刺激因子治疗或空白载体加生理盐水注射治疗。两组患者的特征相似。主要终点是PFS，这在两组中相似(P=0.6)。然而，在研究3年后，Prostvac-VF患者的OS较好，82例患者中有25例(30%)存活，而40例对照组中有7例(17%)存活，中位生存期延长8.5个月(对照组为25.1比16.6个月)，估计风险比为0.56(95%CI，0.37至0.85)，分层对数等级P=0.0061。结论PROSTVAC-VF免疫治疗耐受性良好，与mCRPC男性患者死亡率降低44%，中位OS改善8.5个月有关。这些具有挑衅性的数据提供了具有临床意义的益处的初步证据，但需要在更大的III期研究中得到证实。J Clin Oncol28：1099-1105。(C)2010年美国临床肿瘤学会
PurposeTherapeutic prostate-specific antigen (PSA)-targeted poxviral vaccines for prostate cancer have been well tolerated. PROSTVAC-VF treatment was evaluated for safety and for prolongation of progression-free survival (PFS) and overall survival (OS) in a randomized, controlled, and blinded phase II study.Patients and MethodsIn total, 125 patients were randomly assigned in a multicenter trial of vaccination series. Eligible patients had minimally symptomatic castration-resistant metastatic prostate cancer (mCRPC). PROSTVAC-VF comprises two recombinant viral vectors, each encoding transgenes for PSA, and three immune costimulatory molecules (B7.1, ICAM-1, and LFA-3). Vaccinia-based vector was used for priming followed by six planned fowlpox-based vector boosts. Patients were allocated (2:1) to PROSTVAC-VF plus granulocyte-macrophage colony-stimulating factor or to control empty vectors plus saline injections.ResultsEighty-two patients received PROSTVAC-VF and 40 received control vectors. Patient characteristics were similar in both groups. The primary end point was PFS, which was similar in the two groups (P = .6). However, at 3 years post study, PROSTVAC-VF patients had a better OS with 25 (30%) of 82 alive versus 7 (17%) of 40 controls, longer median survival by 8.5 months (25.1 v 16.6 months for controls), an estimated hazard ratio of 0.56 (95% CI, 0.37 to 0.85), and stratified log-rank P = .0061.ConclusionPROSTVAC-VF immunotherapy was well tolerated and associated with a 44% reduction in the death rate and an 8.5-month improvement in median OS in men with mCRPC. These provocative data provide preliminary evidence of clinically meaningful benefit but need to be confirmed in a larger phase III study. J Clin Oncol 28:1099-1105. (C) 2010 by American Society of Clinical Oncology