NEJM:Tebentafusp治疗可改善转移性葡萄膜黑色素瘤患者总生存期

2021-09-24 MedSci原创 MedSci原创

对于先前未经治疗的转移性葡萄膜黑色素瘤患者,Tebentafusp治疗方案在延长患者总生存期,提高无进展生存率方面优于现有治疗方案

葡萄膜黑色素瘤是成人最常见的眼内癌,约占所有黑色素瘤的3-5%。虽然葡萄膜黑色素瘤起源于黑素细胞,但它不同于皮肤黑色素瘤,具有不同的分子机制、转移模式以及肿瘤免疫微环境。这些差异导致葡萄膜黑色素瘤患者对常规治疗的临床反应不佳,包括免疫检查点抑制,高达50%的葡萄膜黑色素瘤患者会发生转移,特别是肝脏转移,转移后患者预后差,中位总生存期约为1年。Tebentafusp是一种双特异性蛋白质,由可溶性TCR与抗CD3免疫效应器结构域融合而成,近日研究人员考察了Tebentafusp对转移性葡萄膜黑色素瘤患者生存期的影响。

本次研究为III期试验,既往未接受过治疗的hla-a*02:01阳性转移性葡萄膜黑色素瘤患者参与,随机接受Tebentafusp或其他药物,包括Pembrolizumab、Ipilimumab或Dacarbazine,根据患者乳酸脱氢酶水平进行分层,研究的主要终点是总生存率。

378名患者参与研究,其中Tebentafusp组252名患者,对照组126名患者。在意向治疗人群中,Tebentafusp组1年总生存率为73%,对照组为59%(死亡危险比为0.51)。Tebentafusp组的无进展生存率也显著高于对照组(6个月时无进展生存率分别为31% vs 19%;疾病进展或死亡的危险比为0.73)。Tebentafusp组最常见的治疗相关不良事件是细胞因子介导的不良事件和皮肤相关事件,包括皮疹(83%)、发热(76%)和瘙痒(69%)。上述不良事件的发生率和严重程度在前三或四次给药后有所下降,很少导致试验治疗中断(2%)。没有报告任何与治疗相关的死亡案例。

Tebentafusp治疗对生存期及无进展生存期的影响

研究认为,对于先前未经治疗的转移性葡萄膜黑色素瘤患者,Tebentafusp治疗方案在延长患者总生存期,提高无进展生存率方面优于现有治疗方案

原始出处:

Paul Nathan et al. Overall Survival Benefit with Tebentafusp in Metastatic Uveal Melanoma. N Engl J Med,September 23,2021.

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    2022-01-29 sunylz
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  5. 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    2021-09-25 法荣

    学习

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BMC Cancer:司美替尼联合达卡巴嗪用于转移性葡萄膜黑色素瘤的临床研究

背景:葡萄膜黑色素瘤的特点是GNAQ和GNA11突变,导致Ras /Raf/ MEK / ERK通路激活。司美替尼(AZD6244,ARRY-142886)MEK1/2抑制剂,其对葡萄膜黑色素瘤的临床前模型研究中有抗肿瘤效应。针对转移性葡萄膜黑色素瘤的患者以司美替尼单药治疗对比替莫唑胺或达卡巴嗪化疗,随机II期临床试验表明有改善的无进展生存期(PFS)和反应率(RR)。临床前,司美替尼联合烷基化试