Kim Ye Rim, Kim Euichang, Kim Ha Il, Han Seungbong, An Jihyun, Shim Ju Hyun
Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Department of Gastroenterology and Hepatology, Hanyang University College of Medicine, Guri, Republic of Korea.
Liver Cancer. 2025 Jun 12. doi: 10.1159/000546697.
We conducted an updated network meta-analysis to evaluate and identify the optimal first-line treatment for advanced hepatocellular carcinoma (HCC) among all relevant interventional and targeted therapies.
We analyzed 16 phase 2 or 3 randomized controlled trials involving 9,482 patients with metastatic or unresectable HCC published between 2018 and 2024. The trials evaluated 11 systemic agents and 5 interventional treatments in combination with systemic therapy, using either sorafenib or lenvatinib as the control. The primary outcome was overall survival (OS), and secondary outcomes included progression-free survival (PFS) and grade 3-4 adverse events. Subgroup analyses were conducted to assess individual treatment efficacies in specific clinical settings.
Transarterial chemoembolization (TACE) combined with lenvatinib provided the greatest improvement in OS over sorafenib, with a hazard ratio of 0.41 (95% confidence interval, 0.30-0.58), followed by sintilimab + IBI305 (0.57; 0.43-0.75), camrelizumab + rivoceranib (0.62; 0.48-0.80), atezolizumab + bevacizumab (0.66; 0.51-0.85), lenvatinib + pembrolizumab (0.77; 0.62-0.97), and tremelimumab + durvalumab (0.78; 0.64-0.95). These combinations, except for tremelimumab + durvalumab, also showed significantly superior PFS to sorafenib. TACE + lenvatinib was ranked first in OS analyses with the other current standard-of-care regimens (lenvatinib, atezolizumab + bevacizumab, and tremelimumab + durvalumab) as controls. TACE + lenvatinib, sintilimab + IBI305, and atezolizumab + bevacizumab demonstrated consistently significant extension of OS over sorafenib in subsets with portal invasion, extrahepatic metastasis, and hepatitis B. All immunotherapy-based combinations were significantly associated with a higher risk of adverse events than sorafenib.
For advanced HCC, our first-line analysis consistently scored TACE + lenvatinib the best for survival outcomes, followed by various immunotherapy-based combinations. However, the superior efficacy of TACE + lenvatinib should be interpreted with consideration of its derivation from a region with high hepatitis B virus prevalence.
我们进行了一项更新的网络荟萃分析，以评估并确定所有相关介入治疗和靶向治疗中晚期肝细胞癌（HCC）的最佳一线治疗方案。
我们分析了2018年至2024年间发表的16项2期或3期随机对照试验，涉及9482例转移性或不可切除HCC患者。这些试验评估了11种全身用药以及5种与全身治疗联合的介入治疗，以索拉非尼或仑伐替尼作为对照。主要结局为总生存期（OS），次要结局包括无进展生存期（PFS）和3 - 4级不良事件。进行亚组分析以评估特定临床环境中各治疗的疗效。
经动脉化疗栓塞术（TACE）联合仑伐替尼相较于索拉非尼在OS方面改善最大，风险比为0.41（95%置信区间，0.30 - 0.58），其次是信迪利单抗 + IBI305（0.57；0.43 - 0.75）、卡瑞利珠单抗 + 阿伐替尼（0.62；0.48 - 0.80）、阿替利珠单抗 + 贝伐珠单抗（0.66；0.51 - 0.85）、仑伐替尼 + 帕博利珠单抗（0.77；0.62 - 0.97）以及度伐利尤单抗 + 曲美木单抗（0.78；0.64 - 0.95）。除度伐利尤单抗 + 曲美木单抗外，这些联合治疗在PFS方面也显著优于索拉非尼。在以其他当前标准治疗方案（仑伐替尼、阿替利珠单抗 + 贝伐珠单抗以及度伐利尤单抗 + 曲美木单抗）作为对照的OS分析中，TACE + 仑伐替尼排名第一。在有门静脉侵犯、肝外转移和乙型肝炎的亚组中，TACE + 仑伐替尼、信迪利单抗 + IBI305以及阿替利珠单抗 + 贝伐珠单抗相较于索拉非尼均持续显著延长了OS。所有基于免疫治疗的联合治疗相较于索拉非尼均与更高的不良事件风险显著相关。
对于晚期HCC，我们的一线分析始终表明TACE + 仑伐替尼在生存结局方面最佳，其次是各种基于免疫治疗的联合治疗。然而，TACE + 仑伐替尼的卓越疗效应结合其来源于乙型肝炎病毒高流行地区这一情况来解读。
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