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

ABSTRACT Background 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. Methods 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. Results 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 ( I 2 = 55.9%, HR: 0.69, 95% CI: 0.5–0.95, p = 0.023) and PFS ( I 2 = 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 ( I 2 = 65%, RR: 1.09, 95% CI: 0.91–1.31, p = 0.304) or DCR ( I 2 = 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. Conclusion 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.