Lenvatinib Versus Bevacizumab in Combination With Anti-PD-1/PD-L1 Therapy for uHCC: A Meta-Analysis of East Asian...

Systemic therapies have been widely applied in the first-line treatment of patients with unresectable hepatocellular carcinoma (uHCC). Regimens based on programmed cell death 1/ligand 1 (PD-1/PD-L1) inhibitors combined with either bevacizumab or lenvatinib have become first-line treatments, yet the optimal strategy remains controversial. This systematic review and meta-analysis aimed to compare the efficacy and safety of lenvatinib versus bevacizumab, both in combination with PD-1/PD-L1 inhibitors, as first-line therapy for uHCC.

A thorough literature search was performed in PubMed, Web of Science, Embase, CNKI and Wanfang from their inception to August 1, 2025. The primary endpoints were overall survival (OS) and progression-free survival (PFS), whereas secondary endpoints included objective response rate (ORR), disease control rate (DCR) and adverse events (AEs). A meta-analysis using a random effects model was performed to obtain hazard ratio (HRs) and 95% confidence intervals. Statistical analyses were conducted using Stata software.

A total of 10 retrospective cohort studies involving 1659 patients were included. The analysis demonstrated that, compared with the bevacizumab-based regimen, the lenvatinib-based regimen was associated with significantly prolonged OS (I² = 55.9%, HR: 0.69, 95% CI: 0.5-0.95, p = 0.023) and PFS (I² = 45.7%, HR: 0.73, 95% CI: 0.59-0.9, p = 0.004). No significant differences were observed between the two groups in terms of ORR (I² = 65%, RR: 1.09, 95% CI: 0.91-1.31, p = 0.304) or DCR (I² = 77%, RR: 0.99, 95% CI: 0.92-1.06, p = 0.532). Regarding safety, the overall incidence of AEs was comparable between the two groups. However, the lenvatinib-based regimen was associated with a higher incidence of hand-foot skin reaction and neutropenia, whereas the bevacizumab-based regimen carried a higher risk of gastrointestinal haemorrhage.

In this meta-analysis of retrospective studies, lenvatinib plus PD-1/PD-L1 inhibitor regimens were associated with superior OS and PFS compared with bevacizumab plus PD-1/PD-L1 inhibitor regimens as first-line regimen for uHCC in East Asian populations. These findings require confirmation in large-scale, prospective, multinational randomized controlled trials in other populations.