ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1594935
Matching-adjusted indirect comparison of tislelizumab plus lenvatinib versus sintilimab plus bevacizumab biosimilar as first-line treatment for unresectable hepatocellular carcinoma
Provisionally accepted
- 1Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China
- 2West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
- 3Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, Shanghai Municipality, China
- 4BeiGene (Shanghai) Co., Ltd., Shanghai, China
- 5The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
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Background: Programmed cell death-1 / programmed cell death-ligand 1 (PD-[L]1) inhibitors plus bevacizumab (or biosimilars) or tyrosine kinase inhibitors (TKIs) have been widely used for the first-line treatment of patients with unresectable hepatocellular carcinoma (uHCC). However, no head-to-head trials have compared the efficacy outcomes between these two combination regimens. Therefore, an unanchored matching-adjusted indirect comparison (MAIC) was conducted to evaluate the comparative efficacy of tislelizumab plus lenvatinib versus sintilimab plus bevacizumab biosimilar.Methods: Individual patients from the BGB-A317-211 study (NCT 04401800) for tislelizumab plus lenvatinib were adjusted to match the population from the ORIENT-32 (NCT 03794440) for sintilimab plus bevacizumab biosimilar through an unanchored MAIC. Odds Ratios (ORs) of objective response rates (ORR) and disease control rates (DCR), and hazard ratios (HRs) of progression-free survival (PFS) and overall survival (OS) were evaluated to quantify the relative treatment effect between the two treatment regimens after population matching. Sensitivity analyses were performed by sequentially removing one variable in the matching and adjusting the population through simulated treatment comparison (STC).Results: After matching, baseline characteristics were balanced between the tislelizumab plus lenvatinib group (effective sample size [ESS] = 49, ESS/N = 79.03%) and sintilimab plus bevacizumab biosimilar group (N = 380). MAIC analysis indicated that tislelizumab plus lenvatinib group showed significantly higher ORR per RECIST v1.1 (OR = 2.56, 95% CI 1.40-4.63; p = 0.0027), higher DCR (OR = 3.81, 95% CI 1.62-11.20; p = 0.0013), longer PFS (HR = 0.56, 95% CI 0.37-0.84, p = 0.0054), and improved OS (HR = 0.43, 95% CI 0.25-0.74, p = 0.0023), compared to sintilimab plus bevacizumab biosimilar group. Sensitivity analysis by two different methods supported the findings from the primary MAIC analysis.Conclusions: This MAIC analysis demonstrated that tislelizumab plus lenvatinib achieved superior efficacy, with higher ORR and longer PFS and OS compared to sintilimab plus bevacizumab biosimilar in untreated Chinese patients with uHCC.
Keywords: Hepatocellular Carcinoma, matching-adjusted indirect comparison, tislelizumab, Lenvatinib, Sintilimab, bevacizumab
Received: 17 Mar 2025; Accepted: 03 Jun 2025.
Copyright: © 2025 Wang, Liu, Song, Zhao and Zheng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Xin Zheng, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
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