Medical Director, BN ImmunoTherapeutics, 2425 Garcia Ave, Mountain View, CA 94043, USA.
J Clin Oncol. 2010 Mar 1;28(7):1099-105. doi: 10.1200/JCO.2009.25.0597. Epub 2010 Jan 25.
Therapeutic 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.
In 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.
Eighty-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.
PROSTVAC-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.
针对前列腺癌的治疗性前列腺特异性抗原（PSA）靶向痘病毒疫苗具有良好的耐受性。在一项随机、对照、盲法的 II 期研究中，评估了 PROSTVAC-VF 治疗的安全性以及无进展生存期（PFS）和总生存期（OS）的延长情况。
共有 125 例患者参与了多中心疫苗系列试验，这些患者均患有有症状轻微的去势抵抗性转移性前列腺癌（mCRPC）。PROSTVAC-VF 由两种重组病毒载体组成，每个载体均编码 PSA 的转基因，以及三种免疫共刺激分子（B7.1、ICAM-1 和 LFA-3）。使用痘苗病毒载体进行初始接种，随后进行六次计划的禽痘病毒载体加强接种。患者按 2:1 的比例随机分配至 PROSTVAC-VF 加粒细胞-巨噬细胞集落刺激因子组或对照空载体加生理盐水注射组。
82 例患者接受了 PROSTVAC-VF 治疗，40 例患者接受了对照载体治疗。两组患者的特征相似。主要终点是 PFS，两组无差异（P =.6）。然而，在研究后 3 年，PROSTVAC-VF 组患者的 OS 更好，82 例患者中有 25 例（30%）存活，而 40 例对照组中有 7 例（17%）存活，中位生存时间延长了 8.5 个月（对照组为 16.6 个月），估计风险比为 0.56（95%CI，0.37 至 0.85），分层对数秩检验 P =.0061。
PROSTVAC-VF 免疫疗法具有良好的耐受性，与 mCRPC 男性的死亡率降低 44%和中位 OS 延长 8.5 个月相关。这些令人兴奋的数据提供了临床有意义获益的初步证据，但需要在更大的 III 期研究中得到证实。
