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分子靶向药物与免疫抑制剂联合治疗及其他联合治疗在肝细胞癌中的应用
DOI: 10.3969/j.issn.1001-5256.2021.04.043
利益冲突声明：所有作者均声明无利益冲突。
作者贡献声明：欧阳敬中、周艳召、朱瑞利负责文献整理，撰写论文；王征征、陈勋参与文献查询，修改论文；周进学、李庆军负责拟定写作思路，指导撰写文章并最后定稿。
Application of combined therapy with molecular-targeted drugs and immune checkpoint inhibitors and other combined therapies in hepatocellular carcinoma
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摘要: 肝细胞癌(HCC)是最常见的恶性肿瘤之一，发病隐匿，发展迅速，高复发的特点导致HCC患者长期生存面临巨大挑战。分子靶向药物与免疫抑制剂在HCC治疗中成为研究的热点，大量临床试验发现，联合治疗取得了不错的疗效。主要介绍了分子靶向药物与免疫抑制剂联合治疗及其他联合治疗在HCC中的应用，指出当前HCC治疗的最新研究热点在于系统治疗或局部治疗相关的联合治疗。Abstract: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors, and its features of insidious onset, rapid development, and high recurrence bring great challenges to the long-term survival of HCC patients. Molecular-targeted drugs and immune checkpoint inhibitors have become the research hotspots in the treatment of HCC, and a large number of clinical trials have found that combined therapy has achieved a good clinical effect. This article mainly introduces the application of combined therapy with molecular-targeted drugs and immune checkpoint inhibitors and other combined therapies in HCC and points out that combined therapy related to systemic therapy or local therapy has become the latest research hotspot in HCC treatment.
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表 1 关于HCC的联合治疗相关研究
药物 临床试验项目 分期 入组(例) 状态 免疫联合靶向治疗 瑞戈非尼+帕博利珠单抗 NCT03347292 Ⅰ 57 进行中，停止招募 卡博替尼+纳武单抗 NCT03299946 Ⅰ 15 进行中，停止招募 索拉非尼+ PDR001 NCT02988440 Ⅰ 20 完成 仑伐替尼+帕博利珠单抗 NCT03006926 Ⅰ 104 进行中，停止招募 CC-122+纳武单抗 NCT02859324 Ⅰ/Ⅱ 21 完成 FGF401+ PDR001 NCT02325739 Ⅱ 70 完成 INC280+ PDR001 NCT02795429 Ⅱ 90 进行中，停止招募 LY2157299+纳武单抗 NCT02423343 Ⅱ 75 完成 索拉非尼+信迪利单抗/IBI305 NCT03794440 Ⅱ/Ⅲ 566 招募中 贝伐单抗+德瓦鲁单抗 NCT03847428 Ⅲ 888 招募中 贝伐单抗+阿替利珠单抗 NCT04102098 Ⅲ 662 招募中 索拉非尼/卡博替尼+阿替利珠单抗 NCT03755791 Ⅲ 740 招募中 双免疫联合治疗 REGN3767+西米单抗 NCT03005782 Ⅰ 669 招募中 LY3321367+ LY3300054 NCT03099109 Ⅰ 275 进行中，停止招募 伊匹单抗+纳武单抗 NCT01658878 Ⅰ/Ⅱ 1097 进行中，停止招募 Pexa Vec+纳武单抗 NCT03071094 Ⅰ/Ⅱ 30 进行中，停止招募 Relatlimab+纳武单抗 NCT01968109 Ⅰ/Ⅱ 1500 招募中 伊匹单抗+纳武单抗 NCT03222076 Ⅱ 30 进行中，停止招募 伊匹单抗+纳武单抗 NCT03510871 Ⅱ 40 未招募 曲美木单抗/贝伐单抗+德瓦鲁单抗 NCT02519348 Ⅱ 433 进行中，停止招募 曲美木单抗/索拉非尼+德瓦鲁单抗 NCT03298451 Ⅲ 1324 进行中，停止招募 贝伐单抗/索拉非尼+阿替利珠单抗 NCT03434379 Ⅲ 480 进行中，停止招募 其他联合治疗 TACE+纳武单抗 NCT03143270 Ⅰ 14 招募中 TheraSphere+纳武单抗 NCT02837029 Ⅰ 27 进行中，停止招募 Y-90放射性栓塞+帕博利珠单抗 NCT03099564 Ⅰ 30 招募中 Y-90放射性栓塞+纳武单抗 NCT03033446 Ⅱ 40 招募中 SBRT+帕博利珠单抗 NCT03316872 Ⅱ 30 招募中 FOLFOX4+ SHR-1210 NCT03605706 Ⅲ 396 招募中 TACE/贝伐单抗+德瓦鲁单抗 NCT03778957 Ⅲ 600 招募中 注：TACE, 经肝动脉化疗栓塞术；SBRT，立体定向身体放射治疗。 
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