Decraecker Marie, Toulouse Caroline, Blanc Jean-Frédéric
Department of Oncology, Hospital Haut Leveque-CHU Bordeaux, Avenue Magellan, 33604 Pessac, France.
INSERM U1053, BaRITOn, University Victor Segalen, 146 Rue Léo Saignat, 33000 Bordeaux, France.
Cancers (Basel). 2021 Dec 16;13(24):6310. doi: 10.3390/cancers13246310.
The systemic treatment of hepatocellular carcinoma is changing rapidly. Three main classes of treatment are now available. Historically, multi-targeted tyrosine kinase inhibitors (TKIs) (sorafenib and lenvatinib as first-line; regorafenib and cabozantinib as second-line) were the first to show an improvement in overall survival (OS). Anti-vascular endothelial growth factor (anti-VEGF) antibodies can be used in first-line (bevacizumab) or second-line (ramucirumab) combination therapy. More recently, immuno-oncology (IO) has profoundly changed therapeutic algorithms, and the combination of atezolizumab-bevacizumab is now the first-line standard of care. Therefore, the place of TKIs needs to be redefined. The objective of this review was to define the place of TKIs in the therapeutic algorithm at the time of IO treatment in first-line therapy, with a special focus on lenvatinib that exhibits one of the higher anti-tumoral activity among TKI in HCC. We will discuss the place of lenvatinib in first line (especially if there is a contra-indication to IO) but also after failure of atezolizumab and bevacizumab. New opportunities for lenvatinib will also be presented, including the use at an earlier stage of the disease and combination with IOs.
肝细胞癌的系统治疗正在迅速变化。目前有三类主要的治疗方法。从历史上看，多靶点酪氨酸激酶抑制剂（TKIs）（索拉非尼和仑伐替尼作为一线用药；瑞戈非尼和卡博替尼作为二线用药）是首批显示出总生存期（OS）改善的药物。抗血管内皮生长因子（anti-VEGF）抗体可用于一线（贝伐单抗）或二线（雷莫西尤单抗）联合治疗。最近，免疫肿瘤学（IO）深刻改变了治疗方案，阿替利珠单抗-贝伐单抗联合用药现已成为一线标准治疗方案。因此，TKIs的地位需要重新定义。本综述的目的是确定TKIs在一线治疗中IO治疗时的治疗方案中的地位，特别关注在肝癌中抗肿瘤活性较高的TKIs之一仑伐替尼。我们将讨论仑伐替尼在一线治疗中的地位（特别是如果存在IO治疗的禁忌证时），以及在阿替利珠单抗和贝伐单抗治疗失败后的地位。还将介绍仑伐替尼的新机遇，包括在疾病早期的使用以及与IO药物联合使用。
