School of Oncology, Guangxi Medical University, Nanning, Guangxi, 530021, People's Republic of China.
Department of Medical Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, 530021, People's Republic of China.
J Exp Clin Cancer Res. 2019 Nov 4;38(1):447. doi: 10.1186/s13046-019-1412-8.
Molecular targeted therapy for advanced hepatocellular carcinoma (HCC) has changed markedly. Although sorafenib was used in clinical practice as the first molecular targeted agent in 2007, the SHARPE and Asian-Pacific trials demonstrated that sorafenib only improved overall survival (OS) by approximately 3 months in patients with advanced HCC compared with placebo. Molecular targeted agents were developed during the 10-year period from 2007 to 2016, but every test of these agents from phase II or phase III clinical trial failed due to a low response rate and high toxicity. In the 2 years after, 2017 through 2018, four successful novel drugs emerged from clinical trials for clinical use. As recommended by updated Barcelona Clinical Liver cancer (BCLC) treatment algorithms, lenvatinib is now feasible as an alternative to sorafenib as a first-line treatment for advanced HCC. Regorafenib, cabozantinib, and ramucirumab are appropriate supplements for sorafenib as second-line treatment for patients with advanced HCC who are resistant, show progression or do not tolerate sorafenib. In addition, with promising outcomes in phase II trials, immune PD-1/PD-L1 checkpoint inhibitors nivolumab and pembrolizumab have been applied for HCC treatment. Despite phase III trials for nivolumab and pembrolizumab, the primary endpoints of improved OS were not statistically significant, immune PD-1/PD-L1 checkpoint therapy remains to be further investigated. This review summarizes the development and progression of molecular targeted and immune-based checkpoint therapies in HCC.
晚期肝细胞癌（HCC）的分子靶向治疗已经发生了显著变化。尽管索拉非尼于 2007 年作为首个分子靶向药物在临床实践中使用，但 SHARPE 和亚太地区的试验表明，与安慰剂相比，索拉非尼仅将晚期 HCC 患者的总生存期（OS）延长了约 3 个月。在 2007 年至 2016 年的 10 年期间开发了分子靶向药物，但由于反应率低和毒性高，这些药物的每一次 II 期或 III 期临床试验都失败了。在随后的两年，即 2017 年至 2018 年，4 种新型成功药物从临床试验中涌现出来，可供临床使用。根据最新的巴塞罗那临床肝癌（BCLC）治疗算法推荐，仑伐替尼现在可以替代索拉非尼作为晚期 HCC 的一线治疗药物。瑞戈非尼、卡博替尼和雷莫芦单抗是索拉非尼二线治疗耐药、进展或不耐受索拉非尼的晚期 HCC 患者的合适补充药物。此外，在 II 期临床试验中取得了有希望的结果，免疫 PD-1/PD-L1 检查点抑制剂纳武单抗和帕博利珠单抗已应用于 HCC 治疗。尽管纳武单抗和帕博利珠单抗进行了 III 期试验，但 OS 改善的主要终点没有统计学意义，免疫 PD-1/PD-L1 检查点治疗仍需进一步研究。本文综述了 HCC 中分子靶向和免疫检查点治疗的发展和进展。
