S2533 Efficacy and Safety of Atezolizumab Plus Bevacizumab Compared to Tyrosine Kinase Inhibitors (Sorafenib and Lenvatinib) as First-Line Therapy for Unresectable Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis

Introduction: The emergence of immunotherapy-based combinations has led to newer First-line treatment options for unresectable hepatocellular carcinoma. This study aims to compare the efficacy and safety of atezolizumab plus bevacizumab (ATEZO/BEV) versus sorafenib or Lenvatinib (SOR/LEV), by evaluating the outcomes such as overall survival, progression-free survival and adverse events, to determine the optimal therapeutic strategy for patients with advanced hepatocellular carcinoma (HCC). Methods: A systematic search was conducted using PubMed, Google Scholar, and Scopus. PRISMA guidelines were followed. A Boolean expression was constructed to retrieve and select articles from major medical databases. Articles that involved analysis of overall survival and progression-free survival following ATEZO/BEV and SOR/LEV therapy for unresectable hepatocellular carcinoma were included in the study. The difference in mean duration of OS and PFS/DFS following different chemotherapeutic interventions was assessed through the Inverse variance method in R Studio. The Odds ratio of adverse events was assessed using the Mantel-Haenszel method (common effect model), and the Inverse variance method (random effects model) was utilized to analyze the odds ratio. The I2 test was used to assess the heterogeneity. Results: The study included a total of 8 articles with 2459 subjects receiving ATEZO/BEV therapy and 2575 subjects receiving SOR/LEV therapy. The PFS/DFS duration was significantly higher in the ATEZO/BEV group as compared to the SOR/LEV group, indicating better clinical efficacy (Mean difference of PFS = 2.58 (1.58; 3.60), I2 = 99%, P < 0.01). The overall survival duration (MDS = 1.5834 [-1.8846; 5.0515] I2 = 100% P = 0.3709) and the risk of major adverse events did not change significantly between the 2 groups. Conclusion: In patients with Unresectable HCC, atezolizumab combined with bevacizumab resulted in better progression-free survival outcomes than sorafenib/lenvatinib. The overall survival duration and adverse events were similar in both groups, indicating a similar safety profile. Similar clinical efficacy and safety end points make both the drug groups viable as first-line options in the treatment of Unresectable HCC. Further trials should focus on assessing safety end points and hepatotoxicity.