A phase 2 study of tremelimumab in patients with advanced uveal melanoma
A phase 2 study of tremelimumab in patients with advanced uveal melanoma
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DOI：
10.1097/cmr.0000000000000175
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发表时间：
2015-08-01
影响因子：
2.2
通讯作者：
Cheng, Tina
中科院分区：
文献类型：
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作者：
Joshua, Anthony M.;Monzon, Jose G.;Cheng, Tina
与皮肤黑色素瘤相似，葡萄膜黑色素瘤（UM）中也有几种免疫逃逸策略。我们假设这些癌症可以通过增强T细胞活化来对tremelimumab的细胞毒性T淋巴细胞相关抗原-4（CTLA-4）抑制做出反应。这是一项在既往未接受免疫治疗的晚期UM患者中进行的开放标签、多中心II期研究。患者接受曲美木单抗，15 mg/kg，每90天给药一次，最多4个周期。主要终点为6个月无进展生存期（PFS）。次要终点为安全性、持久缓解率、客观缓解率、客观缓解持续时间、完全缓解持续时间和中位总生存期（OS）。11例患者（均患有M1 c疾病）入组，未观察到缓解。中位随访时间为11个月（范围2-36个月）。中位PFS为2.9个月（95%置信区间2.8-3.0），6个月PFS率为9.1%。中位OS为12.8个月（95%置信区间3.8-19.7）。毒性与CTLA-4阻断一致，并且是可管理的。尽管在本研究中观察到的12.8个月的中位OS和可管理的tremelimumab毒性特征似乎是有希望的，但适度的6个月PFS和观察到的缺乏反应导致研究在第一个中期阶段由于无效而停止。到目前为止，没有系统性治疗已经证明了晚期UM患者的生存获益。晚期UM患者的标准治疗应该是临床试验。版权所有（C）2015威科医疗集团All rights reserved.
Similar to cutaneous melanoma, several strategies of immune escape have been documented in uveal melanomas (UMs). We hypothesized that these cancers could respond to cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) inhibition with tremelimumab by potentiating T-cell activation. This was an open-label, multicentre phase 2 study in patients with advanced UM who had not received prior immunotherapy. Patient received tremelimumab at 15mg/kg administered every 90 days for up to four cycles. The primary endpoint was 6-month progression-free survival (PFS). Secondary endpoints were safety, durable response rate, objective response rate, duration of objective response, duration of complete response, and median overall survival (OS). Eleven patients, all with M1c disease, were enrolled with no responses observed. The median follow-up was 11 months (range 2-36 months). The median PFS was 2.9 months (95% confidence interval 2.8-3.0) and the 6-month PFS rate was 9.1%. The median OS was 12.8 months (95% confidence interval 3.8-19.7). Toxicities were consistent with CTLA-4 blockade and were manageable. Although the median OS of 12.8 months and the manageable toxicity profile of tremelimumab observed in this study seem promising, the modest 6-month PFS and the lack of responses observed resulted in the study being stopped due to futility at the first interim stage. To date, no systemic treatment has demonstrated a survival benefit in patients with advanced UM. The standard treatment for patients with advanced UM should be a clinical trial. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved.