Department of Gastrointestinal Medical Oncology, Oncoclínicas, Belo Horizonte, Brazil.
Oncoclínicas, Salvador, Brazil.
JAMA Netw Open. 2021 Dec 1;4(12):e2136128. doi: 10.1001/jamanetworkopen.2021.36128.
Immune checkpoint inhibitors (ICIs) have yielded conflicting results in hepatocellular carcinoma (HCC). The overall effect of ICIs compared with standard therapies in unresectable HCC requires more research.
To estimate the efficacy and safety associated with ICIs compared with standard therapies in patients with unresectable HCC.
PubMed, Cochrane Library, Web of Science, Latin American and Caribbean Health Sciences Literature, and American Society of Clinical Oncology and European Society of Medical Oncology meeting proceedings were systematically searched. Reference lists from studies selected by electronic searching were manually searched to identify additional relevant studies. The search included literature published or presented from February 2010 to February 2020.
From December 2019 to February 2020, independent reviewers evaluated each database, scanning the title, abstract, and keywords of every record retrieved. Full articles were further assessed if the information given suggested that the study was a randomized clinical trial (RCT) comparing ICIs vs standard therapies in the treatment of unresectable HCC.
The full text of the resulting studies and extracted data were reviewed independently according to PRISMA guidelines. Summary hazard ratios (HRs) of overall survival (OS) and progression-free survival (PFS) were calculated by a random-effects model. The likelihood of ICIs being associated with overall response rate (ORR) and treatment-related adverse events (TRAEs) was expressed by odds ratios (ORs) using a random-effects model.
The main outcomes were OS, PFS, ORR, and TRAEs.
Of 1836 studies yielded by the search, 3 were retained, totaling 1657 patients (985 treated with ICIs vs 672 receiving standard treatment). Two studies evaluated ICIs as monotherapy, and 1 study investigated the combination of ICIs with bevacizumab. Compared with standard therapies (sorafenib in first-line therapy or placebo in second-line therapy), ICIs were associated with significantly improved OS (HR, 0.75; 95% CI, 0.62-0.92; P = .006), PFS (HR, 0.74; 95% CI, 0.56-0.97; P = .03), and ORR (OR, 2.82; 95% CI 2.02-3.93; P < .001). The probability of grade 3 or 4 TRAEs was lower with ICIs than with sorafenib (OR, 0.44; 95% CI, 0.20-0.96; P = .04).
This meta-analysis found superior efficacy and safety associated with ICIs compared with standard therapies and highlights the survival benefit associated with the combination of antiangiogenic therapy with ICIs in first-line systemic therapy of unresectable HCC.
免疫检查点抑制剂 (ICI) 在肝细胞癌 (HCC) 中的疗效结果相互矛盾。需要更多的研究来评估 ICI 与不可切除 HCC 的标准治疗相比的总体效果。
评估不可切除 HCC 患者中 ICI 与标准治疗相比的疗效和安全性。
通过系统检索 PubMed、Cochrane 图书馆、Web of Science、拉丁美洲和加勒比健康科学文献以及美国临床肿瘤学会和欧洲肿瘤内科学会会议记录来获取数据。通过电子检索选择的研究的参考文献列表通过手动搜索进行了手动搜索，以确定其他相关研究。搜索包括 2010 年 2 月至 2020 年 2 月发表或展示的文献。
从 2019 年 12 月至 2020 年 2 月，独立评审员评估了每个数据库，扫描每个检索到的记录的标题、摘要和关键字。如果提供的信息表明该研究是一项比较不可切除 HCC 中 ICI 与标准治疗的随机临床试验 (RCT)，则进一步评估全文。
根据 PRISMA 指南，独立审查了研究的全文和提取的数据。使用随机效应模型计算总生存期 (OS) 和无进展生存期 (PFS) 的综合危险比 (HR)。使用随机效应模型，通过优势比 (OR) 表示 ICI 与总缓解率 (ORR) 和治疗相关不良事件 (TRAEs) 相关的可能性。
主要结果是 OS、PFS、ORR 和 TRAEs。
通过搜索得到的 1836 项研究中，有 3 项被保留，共纳入 1657 名患者（985 名接受 ICI 治疗，672 名接受标准治疗）。两项研究评估了 ICI 作为单药治疗，一项研究调查了 ICI 联合贝伐珠单抗的情况。与标准治疗（一线治疗索拉非尼或二线治疗安慰剂）相比，ICI 与显著改善的 OS（HR，0.75；95%CI，0.62-0.92；P = .006）、PFS（HR，0.74；95%CI，0.56-0.97；P = .03）和 ORR（OR，2.82；95%CI，2.02-3.93；P < .001）相关。与索拉非尼相比，ICI 发生 3 级或 4 级 TRAE 的概率较低（OR，0.44；95%CI，0.20-0.96；P = .04）。
这项荟萃分析发现 ICI 与标准治疗相比具有更好的疗效和安全性，并强调了抗血管生成治疗联合 ICI 作为不可切除 HCC 一线全身治疗的生存获益。
