Background: Most phase 3 clinical trials of systemic therapy for first-line unresectable hepatocellular carcinoma (HCC) have failed, with the exception of SHARP, REFLECT, and IMbrave150. We conducted indirect comparisons of therapies evaluated for first-line HCC treatment. Summary: We conducted a systematic review and meta-analysis of treatments for adults with locally advanced or metastatic unresectable HCC and no prior systemic treatment, including atezolizu­mab plus bevacizumab, sorafenib, lenvatinib, nivolumab, selective internal radiotherapy (SIRT), transarterial chemoembolization, and placebo or best supportive care. Randomized controlled trials published from January 1, 2007, to March 12, 2020, were retrieved from MEDLINE and Embase. Qualitative assessment of heterogeneity evaluated study designs, populations, and outcomes. Indirect comparisons used generalized linear models with random effects within a Bayesian framework and informative priors. We calculated relative efficacy estimates with 95% credible intervals (CrIs) and Bayesian posterior probability estimates of atezolizumab-bevacizumab being superior to other treatments. Nine clinical studies with a total of 3,897 participants were identified from 8,783 records and used to build the all-trials evidence network. Indirect comparisons suggested an improved overall survival (OS) with atezolizumab-bevacizumab versus lenvatinib (odds ratio, 0.63 [95% CrI 0.39–1.04]; with 97% Bayesian posterior probability of being superior), nivolumab (0.68 [95% CrI 0.41–1.14]; 94%), sorafenib (0.59 [95% CrI 0.39–0.87]; 99%), SIRT (0.51 [95% CrI 0.32–0.82]; 100%), or placebo/best supportive care (0.40 [95% CrI 0.25–0.64]; 100%). Key Messages: Within the context of indirect comparisons, analyses of OS favored atezolizumab-bevacizumab versus other treatment options for patients with locally advanced or metastatic unresectable HCC.
Liver Cancer

中文翻译：

---

Atezolizumab 加贝伐单抗和其他治疗方案对不可切除肝细胞癌患者的比较疗效：网络荟萃分析

背景：除 SHARP、REFLECT 和 IMbrave150 外，大多数一线不可切除肝细胞癌 (HCC) 全身治疗的 3 期临床试验均失败。我们对评估用于一线 HCC 治疗的疗法进行了间接比较。概括：我们对患有局部晚期或转移性不可切除 HCC 且既往未接受过全身治疗的成人的治疗进行了系统评价和荟萃分析，包括阿特珠单抗加贝伐单抗、索拉非尼、乐伐替尼、纳武单抗、选择性内部放疗 (SIRT)、经动脉化疗栓塞和安慰剂或最好的支持性护理。从 MEDLINE 和 Embase 检索 2007 年 1 月 1 日至 2020 年 3 月 12 日发表的随机对照试验。异质性的定性评估评估了研究设计、人群和结果。间接比较在贝叶斯框架和信息先验中使用具有随机效应的广义线性模型。我们计算了 95% 可信区间 (CrIs) 和贝叶斯后验概率估计的相对疗效估计，atezolizumab-贝伐单抗优于其他治疗。从 8,783 条记录中确定了 9 项临床研究，共有 3,897 名参与者，并用于建立所有试验证据网络。间接比较表明，atezolizumab-bevacizumab 与 lenvatinib（优势比，0.63 [95% CrI 0.39–1.04]；贝叶斯后验概率为 97%）、nivolumab（0.68 [95% CrI 0.41– 1.14]；94%)，索拉非尼 (0.59 [95% CrI 0.39–0.87]；99%)，SIRT (0.51 [95% CrI 0.32–0.82]；100%)，或安慰剂/最佳支持治疗 (0.40 [95% CrI 0.25–0.64]；100%）。783条记录，用于构建全审证据网络。间接比较表明，atezolizumab-bevacizumab 与 lenvatinib（优势比，0.63 [95% CrI 0.39–1.04]；贝叶斯后验概率为 97%）、nivolumab（0.68 [95% CrI 0.41– 1.14]；94%)，索拉非尼 (0.59 [95% CrI 0.39–0.87]；99%)，SIRT (0.51 [95% CrI 0.32–0.82]；100%)，或安慰剂/最佳支持治疗 (0.40 [95% CrI 0.25–0.64]；100%）。783条记录，用于构建全审证据网络。间接比较表明，atezolizumab-bevacizumab 与 lenvatinib（优势比，0.63 [95% CrI 0.39–1.04]；贝叶斯后验概率为 97%）、nivolumab（0.68 [95% CrI 0.41– 1.14]；94%)，索拉非尼 (0.59 [95% CrI 0.39–0.87]；99%)，SIRT (0.51 [95% CrI 0.32–0.82]；100%)，或安慰剂/最佳支持治疗 (0.40 [95% CrI 0.25–0.64]；100%）。关键信息：在间接比较的背景下，对于局部晚期或转移性不可切除的 HCC 患者，OS 分析有利于 atezolizumab-bevacizumab 与其他治疗方案相比。
肝癌