Background: 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.
Methods: 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.
Results: 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.
Conclusion: In patients with MUM, a combination of bevacizumab plus temozolomide achieved a 6-month PFR of 23%.
经验
• 由于转移性葡萄膜黑色素瘤这一罕见肿瘤预后很差, 且其生物学不同于皮肤黑色素瘤, 因此有必要为该肿瘤开展专门的临床试验。
• 对针对 MEK/ERK/MAP 激酶通路的药物进行了检验。
摘要
背景. 贝伐珠单抗在实验模型中可抑制眼黑色素瘤细胞的体外生长和体内肝转移。额外的临床前数据提示贝伐珠单抗与达卡巴嗪联合有潜在的获益。
方法. 本项非对照 II 期研究对贝伐珠单抗 (10 mg/kg, 第8、22天) 联合替莫唑胺 (150 mg/m2, 第 1∼7 天和第 15∼21 天) 治疗 36 例转移性葡萄膜黑色素瘤 (MUM) 患者进行了评价。主要终点为 6 个月无进展率 (PFR)。使用改良两步 Fleming 方案, 欲达到事先确定的 6 个月 PFR 为 40%, 至少需要 10 例/35 例患者。次要终点为无进展生存 (PFS)、总生存 (OS) 和安全性, 肝脏灌注计算机体层摄影 (CT) 评估的反应成像, 以及 VEGF-A 基因多态性对贝伐珠单抗药效学的影响。
结果. 第一步和第二步分析显示分别有 3/17 例及 8/35 例患者 6 个月无进展。最终 6 个月 PFR 为 23% [95%置信区间 (CI): 10∼39], 5 例患者疾病长期稳定 (14%)。中位 PFS 和 OS 分别为 12 周和 10 个月。未观察到预期外的毒性。肝脏灌注 CT 成像无助于评估肿瘤反应, VEGF-A 基因多态性与毒性和生存均无关。
结论. 贝伐珠单抗联合替莫唑胺在 MUM 患者中的 6 个月 PFR 达到了 23%。The Oncologist 2016;21:281–282f
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