中晚期肝细胞癌靶向联合免疫治疗进展

Advances in targeted therapy combined with immunotherapy for advanced hepatocellular carcinoma

IMbrave 150研究开启了免疫治疗联合靶向治疗的大门,随之针对中国患者的Ⅲ期临床研究ORIENTAL-32结果公布,印证了免疫联合靶向的疗效,尤其针对中国患者,生存获益显著。目前诸多程序性死亡受体1/程序性死亡受体-配体1抑制剂联合小分子酪氨酸激酶抑制剂的研究正在进行中,其相应的早期数据提供了非常可观的客观缓解率,为不同病期、不同阶段肝细胞癌的转化治疗/序贯治疗提供了契机,也为新辅助/辅助治疗的深入探索提供了基础。免疫联合治疗已进入3.0版时代,在联合靶向药物的同时,可以在不同阶段实施合理的局部治疗,但目前尚无精准的疗效预测指标,需要缜密结合疾病的自然病程、临床病理学参数、基因组学、影像组学等特征综合考量。免疫联合治疗较之单药免疫或单药靶向治疗,不良反应谱相对复杂,相关性鉴别困难,需要多学科综合诊疗框架下的全程管理、综合判断和及时处置。

The IMbrave 150 study opened the door of immunotherapy combined with targeted therapy, and then the data of ORIENTAL-32, a Phase Ⅲ clinical trial for Chinese patients, was released, which confirmed the efficacy of immunotherapy combined with targeted therapy, especially significant survival benefits in Chinese patients. At present, there are many ongoing studies on PD-1/PD-L1 inhibitors combined with small-molecule tyrosine kinase inhibitors, and their corresponding early data provide a considerable objective response rate, which provides an opportunity for conversion therapy/sequential therapy for hepatocellular carcinoma in different stages and courses, as well as a basis for further exploration of neoadjuvant/adjuvant therapy. Combined immunotherapy has entered the era of version 3.0, in which reasonable local therapy can be implemented at different stages in combination with targeted drugs. However, there are still no accurate predictive indicators for efficacy, and it requires comprehensive consideration of the features such as the natural course of the disease, clinicopathological parameters, genomics, and radiomics. Compared with single-drug immunotherapy or single-drug targeted therapy, immunotherapy combined with targeted therapy had a relatively complex spectrum of adverse reactions and difficult identification of correlation, and whole-process management, comprehensive judgment, and timely treatment should be performed within the framework of multidisciplinary team.