肝动脉灌注化疗联合贝伐珠单抗+信迪利单抗与阿替利珠单抗在晚期肝细胞癌中的疗效与安全性比较

Efficacy and safety of hepatic arterial infusion chemotherapy plus bevacizumab with sintilimab vs. atezolizumab in advanced hepatocellular carcinoma

摘要:

背景与目的 近年来，随着系统治疗的不断进展，肝动脉灌注化疗（HAIC）联合免疫检查点抑制剂及抗血管生成药物在晚期肝细胞癌（HCC）治疗中显示出显著疗效。然而，不同免疫靶点的联合策略（PD-1抑制剂与PD-L1抑制剂）在临床获益和安全性方面的差异尚缺乏直接对比。本研究旨在比较HAIC联合贝伐珠单抗及信迪利单抗（HAIC-BP1）与HAIC联合贝伐珠单抗及阿替利珠单抗（HAIC-BPL）在晚期HCC中的疗效与安全性。方法 回顾性分析2020年1月—2022年12月在中山大学肿瘤防治中心接受HAIC-BP1或HAIC-BPL一线治疗的88例HCC患者。比较两组患者的无进展生存期（PFS）、总生存期（OS）、客观缓解率（ORR）、疾病控制率（DCR）、不良事件（AE），并分析影响PFS的危险因素。结果 共纳入HAIC-BP1组47例和HAIC-BPL组41例，两组患者基线特征差异无统计学意义（均P>0.05）。HAIC-BP1组和HAIC-BPL组的ORR（59.6% vs. 65.9%）和DCR（72.3% vs. 80.5%）差异均无统计学意义（均P>0.05）。中位随访16.3个月后，HAIC-BP1组和HAIC-BPL组的中位OS（21.3个月vs. 22.4个月）及中位PFS（6.7个月vs. 6.2个月）差异均无统计学意义（均P>0.05）。两组AE发生率相近，未见治疗相关死亡。Cox回归分析显示，肿瘤直径>10 cm是PFS的独立危险因素（HR=0.48，95% CI=0.27~0.83，P=0.009）。结论 HAIC-BP1与HAIC-BPL在晚期HCC一线治疗中均具有可比的疗效与良好的安全性，均可作为治疗选择。肿瘤直径>10 cm是PFS的不良预后因素，提示患者分层在临床决策中具有重要意义。

Abstract:

Background and Aims In recent years, with the continuous progress of systemic therapy, hepatic arterial infusion chemotherapy (HAIC) combined with immune checkpoint inhibitors and anti-angiogenic agents has demonstrated significant efficacy in the treatment of advanced hepatocellular carcinoma (HCC). However, direct comparisons between different immunotherapeutic targets, such as PD-1 and PD-L1 inhibitors, in terms of clinical benefit and safety remain limited. This study aimed to compare the efficacy and safety of HAIC plus bevacizumab and sintilimab (HAIC-BP1) versus HAIC plus bevacizumab and atezolizumab (HAIC-BPL) in advanced HCC.Methods A retrospective analysis was conducted on 88 patients with advanced HCC who received first-line HAIC-BP1or HAIC-BPL at Sun Yat-sen University Cancer Center between January 2020 and December 2022. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs) were compared between the two groups. Cox regression analysis was performed to identify prognostic factors affecting PFS.Results A total of 47 patients were included in the HAIC-BP1 group and 41 patients in the HAIC-BPL group, with no statistically significant differences in baseline characteristics between the two groups (all P>0.05). The ORR (59.6% vs. 65.9%) and DCR (72.3% vs. 80.5%) did not significantly differ between the HAIC-BP1 group and the HAIC-BPL group (both P>0.05). After a median follow-up of 16.3 months, there were no significant differences in median OS (21.3 months vs. 22.4 months) or median PFS (6.7 months vs. 6.2 months) between the HAIC-BP1 group and the HAIC-BPL group (both P>0.05). The incidence of AEs was similar, and no treatment-related deaths occurred. Multivariate Cox regression analysis identified tumor diameter >10 cm as an independent adverse prognostic factor for PFS (HR=0.48, 95% CI=0.27-0.83, P=0.009).Conclusion Both HAIC-BP1 and HAIC-BPL demonstrated comparable efficacy and favorable safety profiles as first-line treatment options for advanced HCC. Tumor diameter >10 cm was an independent unfavorable prognostic factor for PFS, underscoring the importance of patient stratification in clinical decision-making.