Remitha Ni Putu Sri Indrani, Dewi Ni Putu Rista Pradnya, Kusuma Komang Wira Ananta, Sasmana I Gede Aswin Parisya, Supadmanaba I Gede Putu, Sindhughosa Dwijo Anargha, Mariadi I Ketut
Faculty of Medicine, Udayana University, Denpasar, Bali, Indonesia.
Department of Biochemistry, Faculty of Medicine, Udayana University, Denpasar, Bali, Indonesia.
Asian Pac J Cancer Prev. 2025 May 1;26(5):1529-1542. doi: 10.31557/APJCP.2025.26.5.1529.
Hepatocellular carcinoma (HCC), the leading form of primary liver cancer, is strongly associated with liver cirrhosis and major risk factors such as hepatitis B and C, alcohol consumption, obesity, and non-alcoholic fatty liver disease. Despite treatment advancements, survival rates for unresectable HCC remain low. Lenvatinib and the combination of atezolizumab and bevacizumab (ATE/BEV) show promise, but further studies are needed to compare their clinical outcomes. This study aims to assess the efficacy and safety of LEN and ATE/BEV in unresectable HCC patients.
This research was conducted using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) strategy. Literature searches were conducted through PubMed, ScienceDirect, Google Scholar, Cochrane Library, SpringerLink, and Ebsco to gather studies on comparing LEN versus ATE/BEV for managing unresectable HCC. The quality assessment was assessed using the Newcastle-Ottawa Scale (NOS). Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR) and treatment-related adverse events (AEs) were evaluated using Review Manager 5.4 and RStudio 2024.04.1.
Twelve retrospective studies were included, comprising 6,620 samples. There was no difference in the OS (HR=0.72; 95%CI: 0.44-1.18, p=0.20), PFS (HR=0.90; 95%CI: 0.75-1.07; p=0.23), ORR (OR=1.16; 95%CI:0.86-1.56; p=0.34) and DCR (OR=1.14; 95%CI:0.97-1.34; p=0.12) between groups. Moreover, in viral and non-viral patients group, LEN showed similar OS and PFS compared with ATE/BEV. In terms of safety, LEN exhibited higher incidences of decreased appetite (OR=2.95; 95%CI:1.12-7.79; p=0.03), diarrhea (OR=2.61; 95%CI:2.06-3.32; p<0.00001), fatigue (OR=1.48; 95%CI:1.27-1.73; P<0.00001), hand-foot syndrome (OR=7.73; 95%CI:4.84-12.33; P<0.00001), and showed lower incidences of increased aspartate aminotransferase (OR=0.44; 95%CI:0.28-0.69; p=0.0004) compared to ATE/BEV. Moreover, LEN showed similar AEs in grade ≥ 3 AEs (OR=1.15; 95%CI:0.29-4.55; p=0.84), hypertension (OR=1.39; 95%CI:0.84-2.28; p=0.20), proteinuria (OR=1.10; 95%CI:0.75-1.60; p=0.63) compared to ATE/BEV.
LEN was found to be non-inferior to ATE/BEV in terms of OS, PFS, ORR, DCR. However, LEN may be associated with a higher incidence of AEs.
肝细胞癌（HCC）是原发性肝癌的主要形式，与肝硬化以及乙型和丙型肝炎、酒精摄入、肥胖和非酒精性脂肪性肝病等主要危险因素密切相关。尽管治疗取得了进展，但不可切除HCC的生存率仍然很低。乐伐替尼以及阿替利珠单抗和贝伐单抗联合用药（ATE/BEV）显示出前景，但需要进一步研究来比较它们的临床疗效。本研究旨在评估乐伐替尼（LEN）和ATE/BEV在不可切除HCC患者中的疗效和安全性。
本研究采用PRISMA（系统评价和Meta分析的首选报告项目）策略进行。通过PubMed、ScienceDirect、谷歌学术、Cochrane图书馆、SpringerLink和Ebsco进行文献检索，以收集比较LEN与ATE/BEV治疗不可切除HCC的研究。使用纽卡斯尔-渥太华量表（NOS）进行质量评估。使用Review Manager 5.4和RStudio 2024.04.1评估总生存期（OS）、无进展生存期（PFS）、客观缓解率（ORR）、疾病控制率（DCR）和治疗相关不良事件（AE）。
纳入12项回顾性研究，共6620个样本。两组之间的OS（风险比[HR]=0.72；95%置信区间[CI]：0.44-1.18，p=0.20）、PFS（HR=0.90；95%CI：0.75-1.07；p=0.23）、ORR（比值比[OR]=1.16；95%CI：0.86-1.56；p=0.34）和DCR（OR=1.14；95%CI：0.97-1.34；p=0.12）无差异。此外，在病毒感染和非病毒感染患者组中，与ATE/BEV相比，LEN显示出相似的OS和PFS。在安全性方面，与ATE/BEV相比，LEN出现食欲下降（OR=2.95；95%CI：1.12-7.79；p=0.03）、腹泻（OR=2.61；95%CI：2.06-3.32；p<0.00001）、疲劳（OR=1.48；95%CI：1.27-1.73;P<0.00001）、手足综合征（OR=7.73；95%CI：4.84-12.33；P<0.00001）的发生率更高，而天门冬氨酸氨基转移酶升高的发生率更低（OR=0.44；95%CI：0.28-0.69；p=0.0004）。此外，与ATE/BEV相比，LEN在≥3级AE（OR=1.15；95%CI：0.29-4.55；p=0.84）、高血压（OR=1.39；95%CI：0.84-2.28；p=0.20）、蛋白尿（OR=1.10；95%CI：0.75-1.60；p=0.63）方面显示出相似的AE发生率。
在OS、PFS、ORR、DCR方面，发现LEN不劣于ATE/BEV。然而，LEN可能与更高的AE发生率相关。
