Department of General Medical Oncology, University Hospitals Leuven, Leuven Cancer Institute, Catholic University Leuven, Leuven, Belgium.
BJU Int. 2011 Sep;108(5):679-86. doi: 10.1111/j.1464-410X.2010.09947.x. Epub 2010 Dec 13.
• To evaluate the efficacy and safety of single-agent AMG 102, an investigational, fully human monoclonal antibody to hepatocyte growth factor/scatter factor (HGF/SF), in renal cell carcinoma (RCC).
• This open-label phase II study included patients ≥ 18 years old with histologically confirmed, advanced or metastatic RCC (mRCC) and Eastern Cooperative Oncology Group performance status 0 to 2. AMG 102 was administered i.v. at 10 or 20 mg/kg once every 2 weeks. • A two-stage design was used at each dose level and the primary endpoint was objective best confirmed response (by Response Evaluation Criteria in Solid Tumours) at any time.
• Sixty-one patients with mRCC enrolled and received AMG 102 (40 at 10 mg/kg; 21 at 20 mg/kg). Overall, 70.5% were men, median age was 59 years (range, 39 to 84 years), and 92% had received previous anti-vascular endothelial growth factor therapy. RCC histologies were: clear cell (75.4%), papillary (11.5%), chromophobe (4.9%) and unclassified (8.2%). • One confirmed partial response occurred at 10 mg/kg, maintained for over 2.5 years; 26 patients (43%) had stable disease, 10 (16%) for ≥ 32 weeks. The median profression-free survival was 3.7 months at 10 mg/kg and 2.0 months at 20 mg/kg. The commonest adverse events were oedema (45.9%), fatigue (37.7%) and nausea (27.9%). Grade 3 or 4 adverse events occurred in 33% of patients, the most common being oedema (9.8%). • Baseline levels of plasma HGF/SF and soluble c-Met as well as archival-tumour c-Met did not correlate with measures of efficacy.
• Single-agent AMG 102 was tolerable, but it is unclear if AMG 102 was growth inhibitory in this population of patients with mRCC.
评估 AMG 102（一种研究性的、全人源单克隆抗体，针对肝细胞生长因子/分散因子（HGF/SF））单药治疗肾细胞癌（RCC）的疗效和安全性。
这项开放标签的 2 期研究纳入了≥18 岁的组织学确诊的晚期或转移性 RCC（mRCC）和东部肿瘤协作组体能状态 0-2 的患者。AMG 102 以 10 或 20mg/kg 的剂量静脉输注，每 2 周一次。每个剂量水平采用两阶段设计，主要终点为任何时间的客观最佳确认缓解（通过实体瘤反应评价标准）。
共 61 例 mRCC 患者入组并接受 AMG 102 治疗（10mg/kg 组 40 例，20mg/kg 组 21 例）。总体而言，70.5%为男性，中位年龄为 59 岁（范围为 39-84 岁），92%接受过抗血管内皮生长因子治疗。RCC 组织学类型为：透明细胞（75.4%）、乳头状（11.5%）、嫌色细胞（4.9%）和未分类（8.2%）。10mg/kg 剂量组有 1 例患者出现确认的部分缓解，缓解持续时间超过 2.5 年；26 例（43%）患者疾病稳定，其中 10 例（16%）稳定≥32 周。10mg/kg 组无进展生存期的中位值为 3.7 个月，20mg/kg 组为 2.0 个月。最常见的不良事件为水肿（45.9%）、乏力（37.7%）和恶心（27.9%）。33%的患者出现 3 级或 4 级不良事件，最常见的是水肿（9.8%）。血浆 HGF/SF 和可溶性 c-Met 以及存档肿瘤 c-Met 的基线水平与疗效测量无关。
单药 AMG 102 可耐受，但尚不清楚 AMG 102 是否对该人群的 mRCC 患者具有生长抑制作用。
