BACKGROUND Advanced hepatocellular carcinoma (HCC) portends a poor prognosis; however recent advances in first-line and second-line treatment options should yield significant improvements in survival. AIM To summarize the evolving landscape of treatment options for patients with advanced HCC. METHODS We reviewed published clinical trials conducted in patients with advanced HCC published in PubMed or presented at national conferences. RESULTS Sorafenib was approved for treatment of unresectable HCC in 2007 and remained the only therapy with proven survival benefit in advanced HCC for several years. Lenvatinib, another tyrosine-kinase inhibitor, was recently shown to have non-inferior survival vs sorafenib and is another first-line treatment option. The tyrosine-kinase inhibitors, regorafenib and cabozantinib, were shown to significantly improve survival in the second-line setting after sorafenib failure. Ramucirumab, a VEGF inhibitor, can also improve survival in the second-line setting among patients with AFP ≥ 400 ng/dL. Phase II data highlight potential durable objective responses with immune checkpoint inhibitors, prompting conditional FDA approval of nivolumab and pembrolizumab in the second-line setting; however, recent phase III data have failed to demonstrate improved survival compared to other treatment options. Ongoing trials are evaluating combination immune checkpoint inhibitor and immune checkpoint inhibitors with tyrosine-kinase inhibitors or VEGF inhibitors in hopes of further increasing objective responses and overall survival in this patient population. CONCLUSION There are several first-line and second-line therapeutic options available for patients with advanced HCC. Further studies are needed to determine how best to select between and sequence the growing number of therapeutic options.

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评论文章：晚期肝细胞癌的新治疗干预措施。


背景晚期肝细胞癌（HCC）预示着预后不良。然而，一线和二线治疗方案的最新进展应该会显着提高生存率。目的 总结晚期 HCC 患者治疗方案的演变。方法 我们回顾了在 PubMed 上发表或在全国会议上发表的针对晚期 HCC 患者进行的临床试验。结果 索拉非尼于 2007 年被批准用于治疗不可切除的 HCC，并且多年来一直是唯一被证明对晚期 HCC 具有生存益处的疗法。另一种酪氨酸激酶抑制剂乐伐替尼（Lenvatinib）最近被证明与索拉非尼相比具有不较差的生存率，是另一种一线治疗选择。酪氨酸激酶抑制剂瑞戈非尼和卡博替尼被证明可以显着提高索拉非尼失败后二线治疗的生存率。 Ramucirumab 是一种 VEGF 抑制剂，在二线治疗中还可以提高 AFP ≥ 400 ng/dL 患者的生存率。 II 期数据强调了免疫检查点抑制剂潜在的持久客观反应，促使 FDA 有条件批准纳武单抗和派姆单抗用于二线治疗；然而，最近的 III 期数据未能证明与其他治疗方案相比生存率有所提高。正在进行的试验正在评估免疫检查点抑制剂组合以及免疫检查点抑制剂与酪氨酸激酶抑制剂或 VEGF 抑制剂的组合，希望进一步提高该患者群体的客观反应和总体生存率。结论 对于晚期 HCC 患者来说，有多种一线和二线治疗选择。 需要进一步的研究来确定如何最好地在越来越多的治疗方案中进行选择和排序。