Wang Kunyuan, Liu Chang, Song Xiaoling, Zhao Na, Zheng Xin
Department of Infectious Diseases and Hepatology, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Front Immunol. 2025 Jun 23;16:1594935. doi: 10.3389/fimmu.2025.1594935. eCollection 2025.
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.
Individual patients from the BGB-A317-211 study (NCT04401800) for tislelizumab plus lenvatinib were adjusted to match the population from the ORIENT-32 (NCT03794440) 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).
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; = 0.0027), higher DCR (OR = 3.81, 95% CI 1.62-11.20; = 0.0013), longer PFS (HR = 0.56, 95% CI 0.37-0.84, = 0.0054), and improved OS (HR = 0.43, 95% CI 0.25-0.74, = 0.0023), compared to sintilimab plus bevacizumab biosimilar group. Sensitivity analysis by two different methods supported the findings from the primary MAIC analysis.
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.
程序性细胞死亡蛋白1/程序性细胞死亡配体1（PD-[L]1）抑制剂联合贝伐单抗（或生物类似药）或酪氨酸激酶抑制剂（TKIs）已广泛用于不可切除肝细胞癌（uHCC）患者的一线治疗。然而，尚无头对头试验比较这两种联合治疗方案的疗效结果。因此，进行了一项非锚定匹配调整间接比较（MAIC），以评估替雷利珠单抗联合仑伐替尼与信迪利单抗联合贝伐单抗生物类似药的相对疗效。
通过非锚定MAIC对来自替雷利珠单抗联合仑伐替尼的BGB-A317-211研究（NCT04401800）的个体患者进行调整，以匹配来自信迪利单抗联合贝伐单抗生物类似药的ORIENT-32（NCT03794440）的人群。评估客观缓解率（ORR）和疾病控制率（DCR）的比值比（OR），以及无进展生存期（PFS）和总生存期（OS）的风险比（HR），以量化人群匹配后两种治疗方案之间的相对治疗效果。通过在匹配中依次去除一个变量并通过模拟治疗比较（STC）调整人群来进行敏感性分析。
匹配后，替雷利珠单抗联合仑伐替尼组（有效样本量[ESS]=49，ESS/N=79.03%）和信迪利单抗联合贝伐单抗生物类似药组（N=380）的基线特征达到平衡。MAIC分析表明，与信迪利单抗联合贝伐单抗生物类似药组相比，替雷利珠单抗联合仑伐替尼组根据RECIST v1.1标准的ORR显著更高（OR=2.56，95%CI 1.40-4.63；P=0.0027），DCR更高（OR=3.81，95%CI 1.62-11.20；P=0.0013），PFS更长（HR=0.56，95%CI 0.37-0.84，P=0.0054），OS有所改善（HR=0.43，95%CI 0.25-0.74，P=0.0023）。两种不同方法的敏感性分析支持了主要MAIC分析的结果。
这项MAIC分析表明，在未经治疗的中国uHCC患者中，与信迪利单抗联合贝伐单抗生物类似药相比，替雷利珠单抗联合仑伐替尼具有更好的疗效，ORR更高，PFS和OS更长。
