I. Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Curr Opin Gastroenterol. 2020 May;36(3):177-183. doi: 10.1097/MOG.0000000000000626.
Despite major therapeutic improvements in most cancer entities, hepatocellular carcinoma (HCC) has remained a dismal disease. In fact, incidence and mortality are increasing in many parts of the world, including the United States. Given that a number of systemic agents has recently been tested positive in phase 3 clinical trials, the objective of this review is to summarize the current treatment landscape for advanced HCC.
Following the positive SHARP trial in 2008, sorafenib has been the only systemic agent for advanced HCC for almost a decade. However, in first line, lenvatinib was tested noninferior to sorafenib, and most recently, the combination of atezolizumab with bevacizumab was tested superior to sorafenib. In second line, regorafenib, cabozantinib, and ramucirumab (the latter for patients with AFP ≥400 ng/ml) have shown prolonged overall survival compared with placebo.
Systemic treatment options for advanced HCC have substantially increased over the past years. The combination of atezolizumab and bevacizumab will likely become the new standard of care as it is the first treatment to report improved overall survival compared with sorafenib and the first, and so far only, positive phase 3 clinical trial for an immune-checkpoint inhibitor-containing regimen in advanced HCC.
尽管大多数癌症实体在治疗上取得了重大进展，但肝细胞癌（HCC）仍然是一种预后不良的疾病。事实上，包括美国在内的世界许多地区，肝癌的发病率和死亡率都在上升。鉴于一些系统药物最近在 3 期临床试验中被证实有效，本综述的目的是总结晚期 HCC 的当前治疗现状。
在 2008 年 SHARP 试验取得阳性结果后，索拉非尼几乎成为晚期 HCC 的唯一系统治疗药物近十年。然而，在一线治疗中，仑伐替尼被证明与索拉非尼非劣效，最近，阿替利珠单抗联合贝伐珠单抗被证明优于索拉非尼。在二线治疗中，regorafenib、卡博替尼和雷莫芦单抗（后者用于 AFP≥400ng/ml 的患者）与安慰剂相比，总生存期延长。
近年来，晚期 HCC 的系统治疗选择有了显著增加。阿替利珠单抗联合贝伐珠单抗可能成为新的标准治疗方法，因为它是第一个报告总生存期优于索拉非尼的治疗方法，也是第一个也是迄今为止唯一的在晚期 HCC 中包含免疫检查点抑制剂方案的阳性 3 期临床试验。
