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比较 PD-L1 与 PD-1 抗体联合仑伐替尼和肝动脉灌注化疗治疗不可切除的肝细胞癌。

Comparing PD-L1 with PD-1 antibodies combined with lenvatinib and hepatic arterial infusion chemotherapy for unresectable hepatocellular carcinoma.

机构信息

Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China.

State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China.

出版信息

Front Immunol. 2024 Oct 23;15:1491857. doi: 10.3389/fimmu.2024.1491857. eCollection 2024.

Abstract

BACKGROUND

A combination of hepatic arterial infusion chemotherapy (HAIC), lenvatinib, and immune checkpoint inhibitors (ICIs) yields a high tumor response rate and survival benefit in unresectable hepatocellular carcinoma (uHCC). However, the selection criteria for different ICIs remain unclear. This study aims to compare the efficacy and safety of PD-1/PD-L1 antibodies combined with HAIC and lenvatinib.

METHODS

This retrospective study included 184 patients with uHCC treated with HAIC+lenvatinib+PD-1/PD-L1 antibody from June 2019 to January 2022. We utilized propensity score matching (PSM) to select and match 60 patients treated with HAIC + durvalumab + lenvatinib (HDL) against 60 patients treated with HAIC + PD-1 antibodies + lenvatinib (HPL) to compare the efficacy and safety profiles of these two groups.

RESULTS

After PSM, the baseline characteristics were well-balanced between the HDL and HPL groups. The overall survival (p = 0.293) and progression-free survival (p = 0.146) showed no significant difference. The objective response rate (ORR) was higher in the HDL group compared to the HPL group according to modified RECIST (74.1% vs. 53.6%, p = 0.022) and RECIST 1.1 (60.3% vs. 41.1%, p = 0.040), respectively. The incidence of grade 3 or 4 adverse events (AEs) was 10.0% and 18.3% (p = 0.191) in the HDL and HPL groups, respectively.

CONCLUSIONS

PD-L1 antibody appears to be a preferable companion in the combination therapy of HAIC + ICIs + lenvatinib compared to PD-1 antibody, showing higher ORR and relatively lower incidence of severe AEs. Further prospective studies involving a larger patient population are warranted.

摘要

背景

肝动脉灌注化疗(HAIC)联合仑伐替尼和免疫检查点抑制剂(ICIs)在不可切除的肝细胞癌(uHCC)中可获得高肿瘤缓解率和生存获益。然而,不同 ICIs 的选择标准仍不清楚。本研究旨在比较 PD-1/PD-L1 抗体联合 HAIC 和仑伐替尼的疗效和安全性。

方法

这是一项回顾性研究,纳入了 2019 年 6 月至 2022 年 1 月期间接受 HAIC+仑伐替尼+PD-1/PD-L1 抗体治疗的 184 例 uHCC 患者。我们采用倾向评分匹配(PSM)选择并匹配 60 例接受 HAIC+度伐利尤单抗+仑伐替尼(HDL)治疗的患者与 60 例接受 HAIC+PD-1 抗体+仑伐替尼(HPL)治疗的患者,比较两组的疗效和安全性。

结果

PSM 后,HDL 组和 HPL 组的基线特征均衡。总体生存(p=0.293)和无进展生存(p=0.146)无显著差异。根据改良 RECIST(74.1%比 53.6%,p=0.022)和 RECIST 1.1(60.3%比 41.1%,p=0.040),HDL 组的客观缓解率(ORR)高于 HPL 组。HDL 组和 HPL 组 3 级或 4 级不良事件(AE)发生率分别为 10.0%和 18.3%(p=0.191)。

结论

与 PD-1 抗体相比,PD-L1 抗体似乎是 HAIC+ICI+仑伐替尼联合治疗的更好选择,具有更高的 ORR 和相对较低的严重 AE 发生率。需要进一步开展涉及更大患者人群的前瞻性研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/799e/11537909/c2ed86b8ff9e/fimmu-15-1491857-g001.jpg

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