Supplementary Material for: Comparative Efficacy of Atezolizumab plus Bevacizumab and Other Treatment Options for Patients with Unresectable Hepatocellular Carcinoma: A Network Meta-Analysis

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.背景：针对一线不可切除肝细胞癌（hepatocellular carcinoma, HCC）的全身治疗相关III期临床试验大多以失败告终，仅SHARP、REFLECT及IMbrave150三项研究除外。我们针对一线肝细胞癌治疗的评估疗法开展了间接比较分析。 摘要：我们针对无既往全身治疗史的局部晚期或转移性不可切除肝细胞癌成年患者的治疗方案开展了系统评价与Meta分析，纳入的治疗方案包括阿替利珠单抗联合贝伐珠单抗、索拉非尼、仑伐替尼、纳武利尤单抗、选择性内放射治疗（selective internal radiotherapy, SIRT）、经动脉化疗栓塞，以及安慰剂或最佳支持治疗。我们从MEDLINE与Embase数据库中检索了2007年1月1日至2020年3月12日发表的随机对照试验。针对异质性的定性评估涵盖研究设计、研究人群与结局指标。间接比较分析采用贝叶斯框架下带随机效应的广义线性模型，并设定信息先验。我们计算了相对疗效估计值及其95%可信区间（credible intervals, CrIs），同时估算了阿替利珠单抗-贝伐珠单抗相较于其他疗法更优的贝叶斯后验概率。我们从8783条文献记录中筛选出9项临床研究，共计3897名受试者，用于构建全试验证据网络。间接比较分析结果显示，相较于仑伐替尼（比值比=0.63，95%CrI：0.39~1.04；贝叶斯后验优效概率为97%）、纳武利尤单抗（0.68，95%CrI：0.41~1.14；94%）、索拉非尼（0.59，95%CrI：0.39~0.87；99%）、选择性内放射治疗（0.51，95%CrI：0.32~0.82；100%）以及安慰剂/最佳支持治疗（0.40，95%CrI：0.25~0.64；100%），阿替利珠单抗-贝伐珠单抗可改善患者的总生存期（overall survival, OS）。 关键信息：在间接比较分析的框架下，针对局部晚期或转移性不可切除肝细胞癌患者，阿替利珠单抗-贝伐珠单抗在总生存期方面优于其他治疗方案。