经动脉化疗栓塞联合仑伐替尼和 PD-1 抑制剂治疗伴有大血管侵犯的晚期肝细胞癌的疗效和安全性。

Efficacy and safety of hepatic arterial infusion chemotherapy combined with lenvatinib and PD-1 inhibitors for advanced hepatocellular carcinoma with macrovascular invasion.

机构信息

Department of Oncology, Second Affiliated Hospital of Nanchang University, Nanchang, 330006, P.R. of China.

Jiangxi Key Laboratory of Clinical and Translational Cancer Research, Nanchang, 330006, P.R. of China.

出版信息

World J Surg Oncol. 2024 May 6;22(1):122. doi: 10.1186/s12957-024-03396-4.

BACKGROUND AND AIMS

The prognosis of hepatocellular carcinoma (HCC) with macrovascular invasion(MaVI)is poor, and the treatment is limited. This study aims to explore the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC), combined with lenvatinib and programmed cell death-1(PD-1) inhibitor in the first-line treatment of HCC with MaVI.

METHODS

From July 2020 to February 2022, we retrospectively analyzed consecutive patients with HCC with MaVI who received hepatic arterial infusion FOLFOX(oxaliplatin, 5-fluorouracil, and leucovorin)combined with lenvatinib and PD-1 inhibitor. The efficacy was evaluated by RECIST 1.1. Kaplan-Meier was used to explore the overall survival and progression-free survival (PFS), and the COX regression model was used to analyze the risk factors of PFS. Adverse events (AEs) were evaluated according to CTCAE5.0.

RESULTS

Thirty-two patients with HCC complicated with MaVI were recruited from the Second Affiliated Hospital of Nanchang University. Among the patients treated with HAIC combined with lenvatinib and PD-1 inhibitor, ten patients (31.25%) got partial response, eighteen patients (56.25%) maintained stable disease and four patients (12.50%) suffered progressive disease during follow-up; and objective response rate was 31.25%, and disease control rate was 87.5%. The median PFS was 179 days. Univariate and multivariate Cox analysis showed that the extrahepatic metastases and Child-Pugh score were independent prognostic factors of PFS. Twenty-two (68.75%) patients suffered adverse reactions. The main AEs were elevated transaminase (46.87%), thrombocytopenia (40.63%), hypoalbuminemia (28.13%), nausea and vomiting (21.88%), leukopenia (18.76%), abdominal pain (15.63%), hypertension (15.63%) and fever (15.63%). There were seven cases (21.88%) that had grade 3 or above AEs; Among them, two cases with elevated transaminase (6.25%), leukopenia, thrombocytopenia, nausea and vomiting, abdominal pain, and diarrhea occurred in one case respectively. Moreover, no treatment-related death was observed.

CONCLUSIONS

Hepatic arterial infusion of FOLFOX combined with lenvatinib and PD-1 inhibitor as the first-line treatment for HCC complicated with MaVI is effective, and adverse reactions are tolerable.

背景与目的

伴大血管侵犯（MaVI）的肝细胞癌（HCC）预后较差，治疗选择有限。本研究旨在探讨肝动脉灌注化疗（HAIC）联合仑伐替尼和程序性细胞死亡蛋白-1（PD-1）抑制剂在伴 MaVI 的 HCC 一线治疗中的疗效和安全性。

方法

2020 年 7 月至 2022 年 2 月，我们回顾性分析了接受肝动脉输注 FOLFOX（奥沙利铂、5-氟尿嘧啶和亚叶酸）联合仑伐替尼和 PD-1 抑制剂治疗伴 MaVI 的 HCC 连续患者。采用 RECIST 1.1 评估疗效。Kaplan-Meier 用于探索总生存期和无进展生存期（PFS），COX 回归模型用于分析 PFS 的风险因素。根据 CTCAE5.0 评估不良事件（AEs）。

结果

从南昌大学第二附属医院招募了 32 例伴 MaVI 的 HCC 患者。在接受 HAIC 联合仑伐替尼和 PD-1 抑制剂治疗的患者中，10 例（31.25%）患者获得部分缓解，18 例（56.25%）患者疾病稳定，4 例（12.50%）患者疾病进展；客观缓解率为 31.25%，疾病控制率为 87.5%。中位 PFS 为 179 天。单因素和多因素 Cox 分析显示，肝外转移和 Child-Pugh 评分是 PFS 的独立预后因素。22 例（68.75%）患者发生不良反应。主要 AEs 为转氨酶升高（46.87%）、血小板减少（40.63%）、低蛋白血症（28.13%）、恶心呕吐（21.88%）、白细胞减少（18.76%）、腹痛（15.63%）、高血压（15.63%）和发热（15.63%）。有 7 例（21.88%）患者发生 3 级及以上 AEs；其中，2 例患者出现转氨酶升高（6.25%），1 例患者出现白细胞减少、血小板减少、恶心呕吐、腹痛、腹泻。此外，没有观察到与治疗相关的死亡。