Abstract：
BACKGROUND: Atezolizumab plus bevacizumab and lenvatinib are the current first-line systematic therapy for unresectable hepatocellular carcinoma (uHCC). However, the selection of initial treatment among the two therapies are controversial. This meta-analysis aims to compare efficacy and safety between atezolizumab plus bevacizumab and lenvatinib.
METHODS: We systematically searched for studies on atezolizumab plus bevacizumab and lenvatinib in the online databases PubMed, Embase, Web of Science and Cochrane Library. The outcome data including overall survival (OS), progression free survival (PFS), tumor response and adverse events (AEs), were independently extracted by two authors in a standardized way.
RESULTS: Eight retrospective cohort studies with 3690 patients (atezolizumab plus bevacizumab: 1680, lenvatinib: 2010) were included in the meta-analysis. The atezolizumab plus bevacizumab group had significant longer PFS [hazard ratio (HR) 0.76, 95% confidence intervals (CI) 0.65-0.88; I squared statistic (I2) = 0.0%, p = 0.590], compared with lenvatinib group but no significant difference in OS (HR 0.87, 95% CI 0.75-1.01; I2 = 0.0%, p = 0.597), objective response rate (ORR) [risk ratio (RR) 0.89, 95% CI 0.79-1.02; I2 = 19.3%, p = 0.283] and disease control rate (DCR) (RR 1.03, 95% CI 0.98-1.09; I2 = 0.0%, p = 0.467) among them. Moreover, patients receiving atezolizumab plus bevacizumab exhibited lower incidences of grade 3/4 AEs than those receiving lenvatinib (RR 0.65, 95% CI 0.51-0.83; I2 = 69.3%, p = 0.003). However, in non-viral patients group, lenvatinib delivered favorable outcomes in OS (HR 1.32, 95% CI 1.04-1.67; I2 = 0.0%, p = 0.380) compared with atezolizumab plus bevacizumab.
CONCLUSIONS: Atezolizumab plus bevacizumab provides potential advantage in efficacy and better safety than lenvatinib in the treatment of uHCC. Lenvatinib is an appropriate effective alternative to atezolizumab plus bevacizumab in patients without viral infecting.
METHODS: We systematically searched for studies on atezolizumab plus bevacizumab and lenvatinib in the online databases PubMed, Embase, Web of Science and Cochrane Library. The outcome data including overall survival (OS), progression free survival (PFS), tumor response and adverse events (AEs), were independently extracted by two authors in a standardized way.
RESULTS: Eight retrospective cohort studies with 3690 patients (atezolizumab plus bevacizumab: 1680, lenvatinib: 2010) were included in the meta-analysis. The atezolizumab plus bevacizumab group had significant longer PFS [hazard ratio (HR) 0.76, 95% confidence intervals (CI) 0.65-0.88; I squared statistic (I2) = 0.0%, p = 0.590], compared with lenvatinib group but no significant difference in OS (HR 0.87, 95% CI 0.75-1.01; I2 = 0.0%, p = 0.597), objective response rate (ORR) [risk ratio (RR) 0.89, 95% CI 0.79-1.02; I2 = 19.3%, p = 0.283] and disease control rate (DCR) (RR 1.03, 95% CI 0.98-1.09; I2 = 0.0%, p = 0.467) among them. Moreover, patients receiving atezolizumab plus bevacizumab exhibited lower incidences of grade 3/4 AEs than those receiving lenvatinib (RR 0.65, 95% CI 0.51-0.83; I2 = 69.3%, p = 0.003). However, in non-viral patients group, lenvatinib delivered favorable outcomes in OS (HR 1.32, 95% CI 1.04-1.67; I2 = 0.0%, p = 0.380) compared with atezolizumab plus bevacizumab.
CONCLUSIONS: Atezolizumab plus bevacizumab provides potential advantage in efficacy and better safety than lenvatinib in the treatment of uHCC. Lenvatinib is an appropriate effective alternative to atezolizumab plus bevacizumab in patients without viral infecting.
摘要：
背景：阿替珠单抗联合贝伐单抗和乐伐替尼是目前不可切除肝细胞癌（uHCC）的一线系统治疗方法。然而,两种疗法中初始治疗的选择存在争议.这项荟萃分析旨在比较阿特珠单抗联合贝伐单抗和乐伐替尼的疗效和安全性。
方法：我们在PubMed在线数据库中系统地搜索了阿司珠单抗联合贝伐单抗和乐伐替尼的研究，Embase,WebofScience和Cochrane图书馆。结果数据包括总生存期(OS)，无进展生存期（PFS），肿瘤反应和不良事件（AE），由两位作者以标准化的方式独立提取。
结果：有3690例患者的8项回顾性队列研究（阿替珠单抗联合贝伐单抗：1680，乐伐替尼：2010）被纳入荟萃分析。阿特珠单抗加贝伐单抗组的PFS明显更长[风险比（HR）0.76，95％置信区间（CI）0.65-0.88；I平方统计（I2）=0.0％，p=0.590],与lenvatinib组相比，但OS无显著差异(HR0.87，95%CI0.75-1.01；I2=0.0%，p=0.597),客观反应率（ORR）[风险比（RR）0.89，95％CI0.79-1.02；I2=19.3％，p=0.283]和疾病控制率（DCR）（RR1.03，95％CI0.98-1.09；I2=0.0％，其中p=0.467）。此外，接受阿替珠单抗联合贝伐单抗的患者3/4级不良事件发生率低于接受乐伐替尼的患者(RR0.65,95%CI0.51-0.83;I2=69.3%,p=0.003)。然而,在非病毒患者组中，lenvatinib在OS中获得了有利的结果(HR1.32，95%CI1.04-1.67；I2=0.0%，p=0.380）与阿妥珠单抗加贝伐单抗相比。
结论：阿替珠单抗联合贝伐单抗在治疗uHCC方面具有潜在的疗效优势和更好的安全性。对于没有病毒感染的患者，Lenvatinib是阿特珠单抗加贝伐单抗的适当有效替代方案。
方法：我们在PubMed在线数据库中系统地搜索了阿司珠单抗联合贝伐单抗和乐伐替尼的研究，Embase,WebofScience和Cochrane图书馆。结果数据包括总生存期(OS)，无进展生存期（PFS），肿瘤反应和不良事件（AE），由两位作者以标准化的方式独立提取。
结果：有3690例患者的8项回顾性队列研究（阿替珠单抗联合贝伐单抗：1680，乐伐替尼：2010）被纳入荟萃分析。阿特珠单抗加贝伐单抗组的PFS明显更长[风险比（HR）0.76，95％置信区间（CI）0.65-0.88；I平方统计（I2）=0.0％，p=0.590],与lenvatinib组相比，但OS无显著差异(HR0.87，95%CI0.75-1.01；I2=0.0%，p=0.597),客观反应率（ORR）[风险比（RR）0.89，95％CI0.79-1.02；I2=19.3％，p=0.283]和疾病控制率（DCR）（RR1.03，95％CI0.98-1.09；I2=0.0％，其中p=0.467）。此外，接受阿替珠单抗联合贝伐单抗的患者3/4级不良事件发生率低于接受乐伐替尼的患者(RR0.65,95%CI0.51-0.83;I2=69.3%,p=0.003)。然而,在非病毒患者组中，lenvatinib在OS中获得了有利的结果(HR1.32，95%CI1.04-1.67；I2=0.0%，p=0.380）与阿妥珠单抗加贝伐单抗相比。
结论：阿替珠单抗联合贝伐单抗在治疗uHCC方面具有潜在的疗效优势和更好的安全性。对于没有病毒感染的患者，Lenvatinib是阿特珠单抗加贝伐单抗的适当有效替代方案。
