Abstract：
BACKGROUND: This meta-analysis was dedicated to evaluating the effectiveness and safety of Atezolizumab plus Bevacizumab (Atez/Bev) and Lenvatinib (LEN) as first-line systematic therapy for unresectable hepatocellular carcinoma (u-HCC).
METHODS: The prospective protocol for this study was registered with the PROSPERO (Registration number: CRD42022356874). Literature searches were conducted in PubMed, EMBASE database Cochrane Library, and Web Science to determine all clinical controlled studies that reported Atez/Bev and LEN for treating u-HCC. We. evaluated as primary end-point overall survival (OS) and progression-free survival (PFS), as well as other outcomes such as tumor response and adverse events (AEs).Quality assessment and data extraction of studies were conducted independently by three reviewers. Mean difference (MD) and odds ratio (OR) with 95% confidence interval (CI) were calculated using a fixed-effects or random-effects model. The meta-analysis was performed with RevMan 5.3 software.
RESULTS: 12 retrospective cohort studies (RCSs) involving a total of 4948 patients were finally included. The results showed that compared with LEN, Atez/Bev can improve the patient\'s PFS (HR = 0.80, 95% CI: 0.72 ~ 0.88; p < 0.0001) and reduce the rate of overall AEs (OR = 0.46 95% CI: 0.38 ~ 0.55, p < 0.00001) and grade ≥ 3 AEs (OR = 0.43; 95% CI: 0.36 ~ 0.51, p < 0.00001), while there is no difference between OS and treatment responses rate (objective response rate, disease control rate, complete response, partial response, progressive disease, and stable disease) between two groups. In addition, the subgroup analysis shows that Atez/Bev can promote the OS of patients with viral hepatitis. (HR = 0.79, 95% CI: 0.67 ~ 0.95; p = 0.01), while LEN has an advantage in improving OS in patients with Child-Pugh grade B liver function (HR = 1.98, 95% CI: 1.50 ~ 2.63; p < 0.00001).
CONCLUSIONS: Current evidence shows that compared with LEN, Atez/Bev has more advantages in PFS and safety in treating u-HCC and can improve the OS of patients with viral. LEN has advantages in improving the OS of patients with grade B liver function. However, more multicenter randomized controlled experiments are needed in the future to verify our results.
METHODS: The prospective protocol for this study was registered with the PROSPERO (Registration number: CRD42022356874). Literature searches were conducted in PubMed, EMBASE database Cochrane Library, and Web Science to determine all clinical controlled studies that reported Atez/Bev and LEN for treating u-HCC. We. evaluated as primary end-point overall survival (OS) and progression-free survival (PFS), as well as other outcomes such as tumor response and adverse events (AEs).Quality assessment and data extraction of studies were conducted independently by three reviewers. Mean difference (MD) and odds ratio (OR) with 95% confidence interval (CI) were calculated using a fixed-effects or random-effects model. The meta-analysis was performed with RevMan 5.3 software.
RESULTS: 12 retrospective cohort studies (RCSs) involving a total of 4948 patients were finally included. The results showed that compared with LEN, Atez/Bev can improve the patient\'s PFS (HR = 0.80, 95% CI: 0.72 ~ 0.88; p < 0.0001) and reduce the rate of overall AEs (OR = 0.46 95% CI: 0.38 ~ 0.55, p < 0.00001) and grade ≥ 3 AEs (OR = 0.43; 95% CI: 0.36 ~ 0.51, p < 0.00001), while there is no difference between OS and treatment responses rate (objective response rate, disease control rate, complete response, partial response, progressive disease, and stable disease) between two groups. In addition, the subgroup analysis shows that Atez/Bev can promote the OS of patients with viral hepatitis. (HR = 0.79, 95% CI: 0.67 ~ 0.95; p = 0.01), while LEN has an advantage in improving OS in patients with Child-Pugh grade B liver function (HR = 1.98, 95% CI: 1.50 ~ 2.63; p < 0.00001).
CONCLUSIONS: Current evidence shows that compared with LEN, Atez/Bev has more advantages in PFS and safety in treating u-HCC and can improve the OS of patients with viral. LEN has advantages in improving the OS of patients with grade B liver function. However, more multicenter randomized controlled experiments are needed in the future to verify our results.
摘要：
背景：这项荟萃分析致力于评估阿替珠单抗联合贝伐单抗（Atez/Bev）和Lenvatinib（LEN）作为不可切除肝细胞癌（u-HCC）的一线系统治疗的有效性和安全性。
方法：本研究的前瞻性方案已在PROSPERO注册（注册编号：CRD42022356874）。文献检索在PubMed进行，EMBASE数据库Cochrane库，和WebScience来确定所有报道Atez/Bev和LEN治疗u-HCC的临床对照研究。我们评估为主要终点总生存期（OS）和无进展生存期（PFS），以及其他结果，如肿瘤反应和不良事件（AE）。研究的质量评估和数据提取由三名评审员独立进行。使用固定效应或随机效应模型计算平均差（MD）和比值比（OR）以及95％置信区间（CI）。Meta分析采用RevMan5.3软件进行。
结果：最终纳入总共4948例患者的12项回顾性队列研究（RCSs）。结果表明,与LEN相比,Atez/Bev可以改善患者的PFS（HR=0.80，95％CI：0.72〜0.88；p<0.0001），降低总体AE（OR=0.4695％CI：0.38〜0.55，p<0.00001）和≥3级AE（OR=0.43；95％CI：0.36〜0.51，p<0.00001），而OS和治疗反应率之间没有差异(客观反应率，疾病控制率,完整的响应,部分响应,进行性疾病,和稳定的疾病)。此外,亚组分析表明，Atez/Bev可以促进病毒性肝炎患者的OS。（HR=0.79，95%CI：0.67~0.95；p=0.01），而LEN在改善Child-PughB级肝功能患者OS方面具有优势(HR=1.98,95%CI:1.50~2.63;p<0.00001)。
结论：目前的证据表明，与LEN相比，Atez/Bev在治疗u-HCC方面具有更多的PFS和安全性，并且可以改善病毒患者的OS。LEN在改善肝功能B级患者的OS方面具有优势。然而,未来还需要更多的多中心随机对照实验来验证我们的结果.
方法：本研究的前瞻性方案已在PROSPERO注册（注册编号：CRD42022356874）。文献检索在PubMed进行，EMBASE数据库Cochrane库，和WebScience来确定所有报道Atez/Bev和LEN治疗u-HCC的临床对照研究。我们评估为主要终点总生存期（OS）和无进展生存期（PFS），以及其他结果，如肿瘤反应和不良事件（AE）。研究的质量评估和数据提取由三名评审员独立进行。使用固定效应或随机效应模型计算平均差（MD）和比值比（OR）以及95％置信区间（CI）。Meta分析采用RevMan5.3软件进行。
结果：最终纳入总共4948例患者的12项回顾性队列研究（RCSs）。结果表明,与LEN相比,Atez/Bev可以改善患者的PFS（HR=0.80，95％CI：0.72〜0.88；p<0.0001），降低总体AE（OR=0.4695％CI：0.38〜0.55，p<0.00001）和≥3级AE（OR=0.43；95％CI：0.36〜0.51，p<0.00001），而OS和治疗反应率之间没有差异(客观反应率，疾病控制率,完整的响应,部分响应,进行性疾病,和稳定的疾病)。此外,亚组分析表明，Atez/Bev可以促进病毒性肝炎患者的OS。（HR=0.79，95%CI：0.67~0.95；p=0.01），而LEN在改善Child-PughB级肝功能患者OS方面具有优势(HR=1.98,95%CI:1.50~2.63;p<0.00001)。
结论：目前的证据表明，与LEN相比，Atez/Bev在治疗u-HCC方面具有更多的PFS和安全性，并且可以改善病毒患者的OS。LEN在改善肝功能B级患者的OS方面具有优势。然而,未来还需要更多的多中心随机对照实验来验证我们的结果.
