Supplementary Material for: Matching-adjusted Indirect Comparison of Arterial FOLFOX and Atezolizumab-Bevacizumab in Unresectable Hepatocellular Carcinoma

Introduction: Previous phase 3 FOHAIC-1 study demonstrated that hepatic arterial infusion chemotherapy (HAIC) of FOLFOX regimen displayed favorable outcomes in advanced hepatocellular carcinoma (HCC) patients, including those with high-risk features (main portal tumor invasion and > 50% liver infiltration). This study aimed to compare the treatment efficacy of HAIC-FOLFOX versus atezolizumab-bevacizumab in HCC patients.

Methods: Individual patient data from the Chinese FOHAIC-1 study and aggregate data from the global IMbrave150 study were used to conduct an anchored matching-adjusted indirect comparison (MAIC). Hazard ratios (HR) and restricted mean survival times (RMST) were calculated to assess survival differences. Landmark analysis was performed to evaluate time-sensitive treatment effects, and simulated treatment comparison (STC) was conducted as sensitivity analysis. Rates of treatment-related adverse events (TRAEs) and TRAE-related discontinuations were also compared.

Results: After matching baseline characteristics, HAIC showed a numerical OS benefit (HR 0.57, 95% CI, 0.30–1.08) and similar PFS benefit (HR 0.79, 95% CI, 0.43–1.47) compared to atezolizumab-bevacizumab in the overall population. In high-risk patients, HAIC demonstrated significantly improved OS (HR 0.30, 95% CI, 0.12–0.72) and 2.89-month longer RMST compared to atezolizumab-bevacizumab (95% CI, 0.15–5.64 months). Additionally, HAIC showed superior PFS (HR 0.25, 95% CI, 0.10–0.64) and 2.88-month longer RMST over atezolizumab-bevacizumab (95% CI, 0.90–4.86). Landmark analysis in high-risk group revealed that HAIC was associated with significant improvements in both OS (HR 0.32, 95% CI, 0.13–0.79) and PFS (HR 0.24, 95% CI, 0.09–0.63) during the 0–12 months following treatment initiation. Sensitivity analysis using the anchored STC analysis yielded consistent results. HAIC was associated with lower rates of grade 3-4 TRAEs and TRAE-related discontinuation in both the overall population and high-risk group.

Conclusion: HAIC treatment provided superior survival benefits and a favorable safety profile compared to atezolizumab-bevacizumab in high-risk HCC patients.

引言：既往Ⅲ期FOHAIC-1研究显示，采用FOLFOX方案的肝动脉灌注化疗（hepatic arterial infusion chemotherapy，HAIC）在晚期肝细胞癌（hepatocellular carcinoma，HCC）患者中展现出良好的治疗结局，包括存在高危特征（主要门静脉癌栓及肝脏浸润面积＞50%）的患者。本研究旨在对比HAIC-FOLFOX与阿替利珠单抗-贝伐珠单抗用于HCC患者的治疗疗效。

方法：本研究采用中国FOHAIC-1研究的个体患者数据，以及全球IMbrave150研究的汇总数据，开展锚定匹配调整间接比较（anchored matching-adjusted indirect comparison，MAIC）。通过计算风险比（hazard ratio，HR）与受限平均生存时间（restricted mean survival time，RMST）评估生存差异；采用地标分析评价时效性治疗效应，并开展模拟治疗比较（simulated treatment comparison，STC）作为敏感性分析；同时对比治疗相关不良事件（treatment-related adverse event，TRAEs）发生率及TRAEs相关停药率。

结果：匹配基线特征后，在整体人群中，相较于阿替利珠单抗-贝伐珠单抗，HAIC展现出数值上的总生存期（overall survival，OS）获益（HR 0.57，95%置信区间0.30~1.08），无进展生存期（progression-free survival，PFS）获益相当（HR 0.79，95%置信区间0.43~1.47）。在高危患者中，相较于阿替利珠单抗-贝伐珠单抗，HAIC的OS显著改善（HR 0.30，95%置信区间0.12~0.72），受限平均生存时间延长2.89个月（95%置信区间0.15~5.64个月）；同时HAIC的PFS更优（HR 0.25，95%置信区间0.10~0.64），受限平均生存时间较对照组长2.88个月（95%置信区间0.90~4.86个月）。高危亚组的地标分析显示，在治疗开始后的0~12个月内，HAIC可显著改善OS（HR 0.32，95%置信区间0.13~0.79）与PFS（HR 0.24，95%置信区间0.09~0.63）。采用锚定STC分析的敏感性分析结果一致。在整体人群与高危亚组中，HAIC的3~4级TRAEs发生率及TRAEs相关停药率均更低。

结论：相较于阿替利珠单抗-贝伐珠单抗，HAIC治疗可为高危HCC患者带来更优的生存获益与良好的安全性特征。