ST LOUIS (MD Consult) - On April 29, 2010, Dendreon announced that the US Food and Drug Administration (FDA) has approved Provenge (sipuleucel-T) for the treatment of asymptomatic or minimally symptomatic metastatic, castrate-resistant (hormone-refractory) prostate cancer (CRPC). Provenge is an autologous cellular immunotherapy designed to induce an immune response against prostatic acid phosphatase, an antigen expressed in most prostate cancers.

Three phase 3 studies involving 737 patients were submitted to the FDA to support the licensure of Provenge. The pivotal study was the IMPACT (IMmunotherapy for Prostate AdenoCarcinoma Treatment) trial, a 512-patient, multicenter, randomized, double-blind, placebo-controlled study that evaluated men with asymptomatic or minimally symptomatic metastatic CRPC. The use of Provenge was associated with extended median survival. Overall, patients in the treatment group experienced a 22.5% reduced risk of death compared with patients in the control group (hazard rate, 0.775). Results from a similarly designed study in men with asymptomatic metastatic CRPC also demonstrated a survival advantage of similar clinical magnitude as the IMPACT study.

The safety of Provenge was evaluated using data from 601 patients with prostate cancer in 4 randomized clinical trials who underwent at least 1 leukapheresis procedure. The most common adverse events (incidence ≥15%) were chills, fatigue, fever, back pain, nausea, joint ache, and headache. Serious adverse events reported in the Provenge group included acute infusion reactions (occurring within 1 day of infusion) and cerebrovascular events. In controlled clinical trials, severe (grade 3) acute infusion reactions were reported in 3.5% of patients in the Provenge group. However, no reports of grade 4 or 5 severity were received. Reactions included chills, fever, fatigue, asthenia, dyspnea, hypoxia, bronchospasm, dizziness, headache, hypertension, muscle ache, nausea, and vomiting.

Dendreon plans to maintain a registry of approximately 1500 patients to further evaluate a small potential safety signal of cerebrovascular events. In 4 randomized clinical trials of Provenge in patients with prostate cancer, cerebrovascular events were observed in 3.5% of patients in the Provenge arm compared with 2.6% of patients in the control arm.

 

圣路易斯(MD Consult)——2010年4月29日，Dendreon公司宣布美国食品药品管理局(FDA)已批准Provenge (sipuleucel-T)用于治疗无症状或症状极轻微的转移性、去势治疗无效的(激素难治性)前列腺癌(CRPC)。Provenge是一种自体细胞免疫疗法，其治疗机制为诱导一种针对前列腺酸性磷酸酶(在大多数前列腺癌中表达的一种抗原)的免疫应答。

上交至FDA的审批材料中有3项III期研究(n=737)支持该药的审批。关键性研究为IMPACT(用于治疗前列腺腺癌的免疫疗法)试验，这是一项多中心、随机、双盲、安慰剂对照研究，共纳入512男患者，这些患者均患有无症状或症状极轻微的转移性CRPC。应用Provenge治疗与中位生存期延长有关。总体上，治疗组患者死亡风险较对照组减少22.5%(危险比，0.775)。一项对无症状的转移性CRPC男性患者进行的、采用相同设计方案的研究亦显示了与IMPACT研究相同程度的生存优势。

Provenge安全性评估所用的数据来自4项随机临床试验中的601例前列腺癌患者，这些病例均至少接受了一次白细胞去除术。最常见的不良事件(发病率≥15%)为寒战、乏力、发热、背痛、恶心、关节痛及头痛。Provenge治疗组报告的严重不良事件包括急性输液反应(发生于输液后24 h内)和脑血管事件。在对照临床试验中，Provenge治疗组患者中有3.5%报告发生重度(3级)急性输液反应，但未收到4级或5级急性输液反应的报告。输液反应包括寒战、发热、乏力、无力、呼吸困难、缺氧、支气管痉挛、头晕、头痛、高血压、肌肉痛、恶心及呕吐。

Dendreon公司计划将保留对大约1,500例患者的登记，以便于进一步评估脑血管事件的小型潜在的安全性信号。在4项对前列腺癌患者应用Provenge治疗的随机临床试验中，Provenge治疗组观察到有3.5%的患者发生脑血管事件，而对照组有2.6%。