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pembrolizumab和循环生物标志物预测晚期不可切除肝细胞癌抗癌反应的2期研究-ag捕鱼平台

文字: 2019-11-13    浏览次数:11001    

backgroundcheckpoint inhibitors have shown modest activity in patients with advanced hepatocellular carcinoma (hcc). herein, the authors report a prospective single-institution clinical/translational phase 2 study of pembrolizumab in patients with advanced hcc and circulating biomarkers closely related to response.

背景:检查点抑制剂在晚期肝细胞癌(hcc)患者中显示出适度的活性。在此,作者进行了一项前瞻性单机构临床/转化2期研究,对pembrolizumab治疗晚期hcc患者以及与治疗反应密切相关的循环生物标志物进行了分析。

 

methodspembrolizumab was administered at a dose of 200 mg intravenously every 3 weeks among patients who may have developed disease progression while receiving, were intolerant of, or refused sorafenib. the circulating levels of cytokines, chemokines, programmed cell death protein 1 (pd-1), programmed death-ligand 1 (pd-l1), and pd-l2 were correlated with response, tumor pd-l1 expression, and other clinicopathological features.

方法:在接受索拉非尼治疗时可能出现疾病进展,以及不耐受或拒绝使用索拉非尼的患者中,每3周静脉注射200mg pembrolizumab。检查与治疗反应、肿瘤组织pd-l1表达及其他临床病理特征相关的细胞因子、趋化因子、程序性死亡受体-1 (pd-1)、程序性死亡受体-配体1 (pd-l1)pd-l2的循环水平。

 

resultsa total of 29 patients were treated and 28 patients were evaluable for response. the most common laboratory grade 3/4 adverse events were increases in aspartate aminotransferase and/or alanine aminotransferase and serum bilirubin, which for the most part were reversible. in terms of efficacy, one patient achieved a complete response and 8 patients achieved partial responses for an overall response rate of 32%.four other patients had stable disease. the median progression-free survival was 4.5 months and the median overall survival was 13 months. response did not correlate with prior sorafenib therapy, pd-l1 tumor staining, or a prior history of hepatitis. correlative studies revealed that high baseline plasma tgf-β levels (≥200 pg/ml) significantly correlated with poor treatment outcomes after pembrolizumab. tumor pd-l1 and plasma pd-l1/pd-1 levels were associated with plasma ifn-γ or il-10.

结果:共有29例患者接受治疗,28例患者可进行治疗反应评价。最常见的实验室3/4级不良事件是天冬氨酸转氨酶和/或丙氨酸转氨酶和血清胆红素的增加,这些情况大多是可逆的。在疗效方面,1例患者完全缓解,8例患者部分缓解,总缓解率为32%。另外4例患者病情稳定。中位无进展生存期为4.5个月,中位总生存期为13个月。治疗反应与先前索拉非尼治疗、pd-l1肿瘤染色或肝炎病史无关。相关研究显示,基线血浆tgf-β水平高(≥200 pg / ml)pembrolizumab治疗结果差显著相关。肿瘤组织pd-l1和血浆pd-l1 / pd-1水平与血浆ifn-γ il-10相关。

 

conclusions:pembrolizumab was found to demonstrate activity in patients with advanced hcc. toxicity generally was tolerable and reversible. a set of immunological markers in blood plasma as well as pd-l1 staining indicated that baseline tgf-β could be a predictive biomarker for response to pembrolizumab.

结论pembrolizumab在晚期hcc患者中具有活性。毒性一般是可耐受和可逆的。一组血浆免疫标记及pd-l1染色试验表明,基线tgf-β可能是pembrolizumab治疗反应的预测性生物标志物。