Atezolizumab plus bevacizumab versus lenvatinib as first-line therapy for advanced hepatocellular carcinoma: A systematic review and meta-analysis.

Aim of the study: Studies comparing atezolizumab plus bevacizumab (ATE/BEV) vs. lenvatinib (LEN) for advanced hepatocellular carcinoma (aHCC) have shown conflicting results. With this background, we aimed to collate the available evidence comparing ATE/BEV and LEN in aHCC.

Material and methods: A comprehensive search of three databases was conducted from inception to November 2022 for studies comparing ATE/BEV with LEN for managing aHCC. Results were presented with their 95% confidence intervals (95% CI) as the hazard ratio (HR) for time-to-event outcomes or odds ratios (OR) for dichotomous outcomes.

Results: A total of 8 studies were included. On analysis of matched cohorts, there was no difference in the objective response rate (ORR) (adjusted odds ratio [aOR] = 1.15, 95% CI: 0.83-1.61) or disease control rate (DCR) (aOR = 0.83, 95% CI: 0.49-1.38) between groups. Three studies reported a significantly longer progression-free survival (PFS) with ATE/LEN, while one reported a longer PFS with LEN. The adjusted hazard ratio (aHR) for PFS available from three studies was comparable (HR = 1.06, 95% CI: 0.75-1.50). Data were insufficient to carry out a formal analysis for overall survival (OS), but none of the studies reported any difference in OS. On comparison of overall adverse events (AE) and ≥ grade 3 AE, there was no difference in the overall analysis, but higher risk of AE with LEN on sensitivity analysis.

Conclusions: Based on the currently available literature, LEN was found to be non-inferior to ATE/BEV in terms of ORR, DCR, and PFS. However, LEN may be associated with a higher incidence of AEs. Further head-to-head trials are required to demonstrate the superiority of ATE/BEV over LEN.