Background In 2020, atezolizumab-bevacizumab became the new standard of care (SOC) for first-line unresectable hepatocellular carcinoma (HCC) patients, following a decade where sorafenib was the preferred first-line treatment. In the last few years, a number of novel systemic treatments with non-inferiority and superiority to sorafenib have been approved as first-line treatments. Objectives The objective of this systematic literature review (SLR) and network meta-analysis (NMA) was to compare randomised controlled trial evidence for atezolizumab-bevacizumab with globally relevant pharmacological comparators for first-line treatment of patients with unresectable HCC. Methods Randomised controlled trials investigating first-line treatment of HCC in adults with no prior systemic treatment were eligible for inclusion into the SLR and were retrieved from Embase, MEDLINE, and Evidence-Based Medicine (EBM) Reviews. Interventions of interest for the NMA included atezolizumab-bevacizumab, sorafenib, lenvatinib, durvalumab (including in combination with tremelimumab), cabozantinib (including in combination with atezolizumab), camrelizumab (including in combination with rivoceranib), pembrolizumab (including in combination with lenvatinib), and tislelizumab. Random effects NMA was conducted for survival endpoints within a Bayesian framework with an informative prior distribution for between-study heterogeneity. The hazard ratios for relative treatment effect were estimated with 95% credible intervals (CrIs). Results The SLR identified 49 studies, of which eight formed a connected evidence network permitting the indirect treatment comparison of atezolizumab-bevacizumab with comparators of interest. The indirect comparisons suggested an improved overall survival (OS) with atezolizumab-bevacizumab versus most comparators. All indirect treatment comparison results for atezolizumab-bevacizumab included the null value within the 95% CrI (n = 1) for OS and progression-free survival (PFS). Conclusions The results of the NMA indicate atezolizumab-bevacizumab is associated with superior or comparable OS and PFS together with a manageable safety profile compared with globally relevant comparators in the unresected HCC indication. The findings support that atezolizumab-bevacizumab remains SOC for the management of first-line unresectable HCC patients.

中文翻译：

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Atezolizumab 联合贝伐珠单抗一线治疗肝细胞癌患者：系统文献综述和荟萃分析。


背景 2020 年，阿替利珠单抗-贝伐珠单抗成为一线不可切除肝细胞癌 （HCC） 患者的新护理标准 （SOC），此前十年索拉非尼是首选的一线治疗。在过去的几年里，许多不劣于和优于索拉非尼的新型全身治疗已被批准作为一线治疗。目的 本系统文献综述 （SLR） 和网状荟萃分析 （NMA） 的目的是将 atezolizumab-bevacizumab 的随机对照试验证据与全球相关的药理学对照对照对照药物用于不可切除 HCC 患者的一线治疗进行比较。方法 调查既往未接受过全身治疗的成人 HCC 一线治疗的随机对照试验符合纳入 SLR 的条件，并从 Embase、MEDLINE 和循证医学 （EBM） 综述中检索。NMA 感兴趣的干预措施包括 atezolizumab-bevacizumab、sorafenib、lenvatinib、durvalumab（包括与 tremelimumab 联合使用）、cabozantinib（包括与 atezolizumab 联合使用）、camrelizumab（包括与 rivoceranib 联合使用）、pembrolizumab（包括与 lenvatinib 联合使用）和替雷利珠单抗。在贝叶斯框架内对生存终点进行随机效应 NMA，研究间异质性具有信息丰富的先验分布。相对治疗效果的风险比是用 95% 可信区间 （CrI） 估计的。结果 SLR 确定了 49 项研究，其中 8 项形成了一个连接的证据网络，允许将 atezolizumab-bevacizumab 与感兴趣的对照药物进行间接治疗比较。 间接比较表明，与大多数对照组相比，atezolizumab-bevacizumab 的总生存期 （OS） 有所改善。atezolizumab-bevacizumab 的所有间接治疗比较结果包括 OS 和无进展生存期 （PFS） 在 95% CrI （n = 1） 内的零值。结论 NMA 的结果表明，在未切除的 HCC 适应症中，与全球相关的对照组相比，atezolizumab-bevacizumab 具有优于或相当的 OS 和 PFS 以及可管理的安全性。研究结果支持 atezolizumab-bevacizumab 仍然是治疗一线不可切除 HCC 患者的 SOC。