Efficacy and Safety of Lenvatinib versus Atezolizumab Plus Bevacizumab in the Treatment of Unresectable Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis
Bibliographic record
Abstract
INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.015 | 0.032 |
| Meta-epidemiology (narrow) | 0.003 | 0.002 |
| Meta-epidemiology (broad) | 0.023 | 0.045 |
| Bibliometrics | 0.008 | 0.008 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.002 | 0.002 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".