Piperno-Neumann Sophie, Diallo Alhassane, Etienne-Grimaldi Marie-Christine, Bidard François-Clément, Rodrigues Manuel, Plancher Corine, Mariani Pascale, Cassoux Nathalie, Decaudin Didier, Asselain Bernard, Servois Vincent
Department of Medical Oncology, Institut Curie, Paris, France
Department of Biostatistics, Institut Curie, Paris, France.
Oncologist. 2016 Mar;21(3):281-2. doi: 10.1634/theoncologist.2015-0501. Epub 2016 Feb 24.
In experimental models, bevacizumab suppressed in vitro growth and in vivo hepatic metastasis of ocular melanoma cells. Additional preclinical data suggested a potential benefit when combining bevacizumab with dacarbazine.
This noncomparative phase II study evaluated a combination of bevacizumab (10 mg/kg on days 8 and 22) with temozolomide (150 mg/m(2) on days 1-7 and 15-21) in 36 patients with metastatic uveal melanoma (MUM). The primary endpoint was the progression-free rate (PFR) at 6 months. Using a modified 2-step Fleming plan, at least 10 of 35 patients were required to support a predefined PFR at 6 months of 40%. Secondary objectives were progression-free survival (PFS), overall survival (OS), and safety; liver perfusion computed tomography (CT) for response imaging; and impact of VEGF-A gene polymorphisms on bevacizumab pharmacodynamics.
First- and second-step analyses revealed nonprogression at 6 months in 3 of 17 and 8 of 35 patients, respectively. Finally, the 6-month PFR was 23% (95% confidence interval [CI]: 10-39), with long-lasting stable disease in 5 patients (14%). Median PFS and OS were 12 weeks and 10 months, respectively. No unexpected toxicity occurred. Liver perfusion CT imaging was not useful in assessing tumor response, and VEGF-A gene polymorphisms were not correlated with toxicity or survival.
In patients with MUM, a combination of bevacizumab plus temozolomide achieved a 6-month PFR of 23%.
在实验模型中，贝伐单抗可抑制眼黑色素瘤细胞的体外生长及体内肝转移。其他临床前数据表明，贝伐单抗与达卡巴嗪联合使用可能有益。
本非对照II期研究评估了贝伐单抗（第8天和第22天，10mg/kg）与替莫唑胺（第1 - 7天和第15 - 21天，150mg/m²）联合应用于36例转移性葡萄膜黑色素瘤（MUM）患者的情况。主要终点为6个月时的无进展率（PFR）。采用改良的两步法弗莱明方案，35例患者中至少需要10例支持预定的6个月PFR为40%。次要目标为无进展生存期（PFS）\总体生存期（OS）和安全性；采用肝脏灌注计算机断层扫描（CT）进行疗效成像；以及VEGF - A基因多态性对贝伐单抗药效学的影响。
第一步和第二步分析分别显示，17例患者中有3例、35例患者中有8例在6个月时未进展。最终，6个月PFR为23%（95%置信区间[CI]：10 - 39），5例患者（14%）病情长期稳定。中位PFS和OS分别为12周和10个月。未发生意外毒性。肝脏灌注CT成像对评估肿瘤反应无用，VEGF - A基因多态性与毒性或生存期无关。
在MUM患者中，贝伐单抗加替莫唑胺联合方案的6个月PFR为23%。
