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Comparative Study
. 2025 May 23:16:1573098.
doi: 10.3389/fimmu.2025.1573098. eCollection 2025.

Lenvatinib versus bevacizumab when combined with PD-1/L1 inhibitor and hepatic arterial infusion chemotherapy in unresectable hepatocellular carcinoma

Lichang Huang #  1 , Yujie Xu #  2 , Na Liu #  1 , Hailong Chen #  3 , Zichao Wu  1 , Qijiong Li  1 , Minqiang Lu  2 , Wei Wei  1 , Yaojun Zhang  1 , Minshan Chen  1 , Li Xu  1 , Ming Shi  1 , Zhicheng Lai  1
Affiliations
Comparative Study

Lenvatinib versus bevacizumab when combined with PD-1/L1 inhibitor and hepatic arterial infusion chemotherapy in unresectable hepatocellular carcinoma

Lichang Huang et al. Front Immunol. .

Abstract

Introduction: The combination of anti-angiogenic agents, PD-1/L1 inhibitors, and hepatic arterial infusion chemotherapy (HAIC) has emerged as an important strategy for unresectable hepatocellular carcinoma (uHCC), yet comparative data on efficacy and safety between different anti-angiogenic agents (lenvatinib [LenHAP] or bevacizumab [BevHAP]) remain lacking, especially in patients with potential resectable features (PotenR).

Methods: This retrospective study included patients from 3 hospitals. Included patients received LenHAP or BevHAP as the first-line treatment. The overall survival (OS), progression-free survival (PFS), objective response rate (ORR), conversion resection rate (CRR) and adverse events (AE) were compared.

Results: We included 108 uHCC patients in each group after propensity score matching (PSM), of which PotenR patients accounted for 34.3%. Compared with BevHAP group, the LenHAP group demonstrated significantly prolonged median PFS (12.6 vs. 8.1 months; HR, 0.64; 95% CI, 0.46-0.90; p=0.0085), with a trend toward improved OS (26.4 vs. 19.6 months; HR, 0.71; 95% CI, 0.41-1.1; p=0.091). PotenR patients receiving LenHAP achieved superior outcomes, including markedly extended OS (both not reached in median, p=0.018), PFS (19.8 vs. 11.5, months, p=0.0067), and higher conversion resection rates (52.6% vs. 25.0%, p=0.015). Both regimens showed comparable safety profiles, with similar frequencies of grade 3-4 adverse events (47.2% vs. 39.8%, p=0.27) and serious adverse events (4.6% vs. 8.3%, p=0.27).

Conclusions: LenHAP might offer enhanced clinical benefits over BevHAP in uHCC, particularly for PotenR patients, while maintaining equivalent tolerability.

Keywords: bevacizumab; combination therapy; hepatocellular carcinoma; lenvatinib; potential resectable.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Flow chart. AFP, alpha-fetoprotein; HAIC, hepatic arterial infusion chemotherapy; HCC, hepatocellular carcinoma; HVTT, hepatic vein/inferior vena cava tumor thrombus; ICI, Immune checkpoint inhibitors; PD-1, programmed cell death protein 1; PD-L1, programmed cell death 1 ligand 1; PSM, propensity score matching; PVTT, portal vein invasion.
Figure 2
Figure 2
Survival analysis and duration of tumor response. (A) Kaplan-Meier curves of overall survival and progression-free survival (B). (C) Duration of overall tumor response per RECIST v1.1. (D). Duration of intrahepatic tumor response per RECIST v1.1.
Figure 3
Figure 3
Survival analysis of patients who received sintilimab and PotenR patients. (A) Kaplan-Meier curves of overall survival and progression-free survival (B) in patients received sintilimab. (C) Kaplan-Meier curves of overall survival and progression-free survival (D) in PotenR patients. CI, confidence interval; HR. hazard ratio.
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