Overall Survival Benefit with Tebentafusp in Metastatic Uveal Melanoma
Overall Survival Benefit with Tebentafusp in Metastatic Uveal Melanoma
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DOI：
10.1056/nejmoa2103485
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发表时间：
2021-09-23
影响因子：
158.5
通讯作者：
Piperno-Neumann, Sophie
中科院分区：
文献类型：
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作者：
Nathan, Paul;Hassel, Jessica C.;Piperno-Neumann, Sophie
背景 葡萄膜黑色素瘤是一种与皮肤黑色素瘤不同的疾病，肿瘤突变负荷低，转移性葡萄膜黑色素瘤患者的 1 年总生存率约为 50%。缺乏显示全身治疗已证实总体生存获益的数据。 Tebentafusp 是一种双特异性蛋白，由与抗 CD3 效应物融合的亲和力增强的 T 细胞受体组成，可以将 T 细胞重定向到目标糖蛋白 100 阳性细胞。方法 在这项开放标签的 3 期试验中，我们以 2:1 的比例随机分配既往未经治疗的 HLA-A*02:01 阳性转移性葡萄膜黑色素瘤患者接受 tebentafusp（tebentafusp 组）或研究者选择的单药派姆单抗、伊匹单抗或达卡巴嗪治疗（对照组），并根据乳酸脱氢酶水平进行分层。主要终点是总生存期。结果共有378名患者被随机分配到tebentafusp组（252名患者）或对照组（126名患者）。 tebentafusp 组的 1 年总生存率为 73%，对照组为 59%（死亡风险比，0.51；95% 置信区间 [CI]，0.37 至 0.71；P
Background Uveal melanoma is a disease that is distinct from cutaneous melanoma, with a low tumor mutational burden and a 1-year overall survival of approximately 50% in patients with metastatic uveal melanoma. Data showing a proven overall survival benefit with a systemic treatment are lacking. Tebentafusp is a bispecific protein consisting of an affinity-enhanced T-cell receptor fused to an anti-CD3 effector that can redirect T cells to target glycoprotein 100-positive cells. Methods In this open-label, phase 3 trial, we randomly assigned previously untreated HLA-A*02:01-positive patients with metastatic uveal melanoma in a 2:1 ratio to receive tebentafusp (tebentafusp group) or the investigator's choice of therapy with single-agent pembrolizumab, ipilimumab, or dacarbazine (control group), stratified according to the lactate dehydrogenase level. The primary end point was overall survival. Results A total of 378 patients were randomly assigned to either the tebentafusp group (252 patients) or the control group (126 patients). Overall survival at 1 year was 73% in the tebentafusp group and 59% in the control group (hazard ratio for death, 0.51; 95% confidence interval [CI], 0.37 to 0.71; P