Sun Weijing, Cabrera Roniel
University of Kansas School of Medicine, Kansas City, KS, USA.
Univesity of Kansas Cancer Center, 2330 Shawnee Mission Pkwy, Suite 210, Westwood, KS, 66205, USA.
J Gastrointest Cancer. 2018 Jun;49(2):107-115. doi: 10.1007/s12029-018-0065-8.
To date, sorafenib, a multiple tyrosine kinase inhibitor, is the only systemic agent approved by the FDA in the first-line treatment of patients with unresectable hepatocellular carcinoma (HCC). Several other tyrosine kinase-inhibiting agents have been investigated in the first-line setting, either alone (sunitinib, brivanib, linifanib, and lenvatinib) or in combination with sorafenib (erlotinib and doxorubicin) in phase 3 trials. However, none of these studies demonstrated an improvement in survival over sorafenib. Many agents have also been tested in patients with HCC whose disease has progressed on sorafenib, but regorafenib is the only one to have demonstrated efficacy in this setting in a randomized, phase 3 trial. There were no clear survival benefits shown with everolimus, brivanib, or ramucirumab as second-line therapy. Nivolumab has also shown promising efficacy in patients with HCC who progressed on sorafenib, which was recently granted approval by the FDA, although larger confirmative trials may be considered. The treatment landscape for patients with advanced unresectable hepatocellular tumors has remained fairly static for the past 10 years, with multiple failed trials yield little change in the way these patients might be treated. However, recent findings for regorafenib, lenvatinib, and nivolumab have led to the most significant changes in the treatment paradigm in years.
迄今为止，多靶点酪氨酸激酶抑制剂索拉非尼是美国食品药品监督管理局（FDA）批准用于一线治疗不可切除肝细胞癌（HCC）患者的唯一全身治疗药物。在一线治疗中，已经对其他几种酪氨酸激酶抑制剂进行了研究，这些研究在3期试验中单独使用（舒尼替尼、布立尼布、利尼伐尼和乐伐替尼）或与索拉非尼联合使用（厄洛替尼和阿霉素）。然而，这些研究均未证明在生存期方面比索拉非尼有改善。许多药物也在索拉非尼治疗后病情进展的HCC患者中进行了测试，但瑞戈非尼是唯一在随机3期试验中证明在这种情况下有效的药物。依维莫司、布立尼布或雷莫西尤单抗作为二线治疗未显示出明显的生存获益。纳武单抗在索拉非尼治疗后病情进展的HCC患者中也显示出有前景的疗效，尽管可能需要考虑进行更大规模的验证性试验，但该药物最近已获得FDA批准。在过去10年中，晚期不可切除肝细胞肿瘤患者的治疗格局一直相当稳定，多项试验失败，这些患者的治疗方式几乎没有变化。然而，最近关于瑞戈非尼、乐伐替尼和纳武单抗的研究结果带来了多年来治疗模式最显著的变化。
