Evaluation of the efficacy and safety of TACE combined with anlotinib and sintilimab in the treatment of patient with CNLC stage ⅡB-ⅢB liver cancer

Gang TONG; Yang HUA; Wei PENG; Ju ZHAO; Junwen HU

doi:10.19401/j.cnki.1007-3639.2025.05.006

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Evaluation of the efficacy and safety of TACE combined with anlotinib and sintilimab in the treatment of patient with CNLC stage ⅡB-ⅢB liver cancer

Original article | 更新时间：2025-12-31

- Evaluation of the efficacy and safety of TACE combined with anlotinib and sintilimab in the treatment of patient with CNLC stage ⅡB-ⅢB liver cancer
- China Oncology Vol. 35, Issue 5, Pages: 478-484(2025)
- 作者机构：
  
  宜宾市第三人民医院肿瘤科，四川宜宾 644000
- 作者简介：
- 基金信息：
  
  Clinical Research of Sichuan Anti-Cancer Association (Qilu)(XH2023 105);Yibin Science and Technology Plan Project(2023SF003)
- DOI：10.19401/j.cnki.1007-3639.2025.05.006
  CLC： R735.7
- Received：03 November 2024，
  
  Revised：2025-03-26，
  
  Published：30 May 2025
- 稿件说明：
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Gang TONG, Yang HUA, Wei PENG, et al. Evaluation of the efficacy and safety of TACE combined with anlotinib and sintilimab in the treatment of patient with CNLC stage ⅡB-ⅢB liver cancer[J]. China Oncology, 2025, 35(5): 478-484.
DOI：

Gang TONG, Yang HUA, Wei PENG, et al. Evaluation of the efficacy and safety of TACE combined with anlotinib and sintilimab in the treatment of patient with CNLC stage ⅡB-ⅢB liver cancer[J]. China Oncology, 2025, 35(5): 478-484. DOI： 10.19401/j.cnki.1007-3639.2025.05.006.

摘要

背景与目的：

中国是一个肝癌高发病率和高死亡率的国家。2022年，中国肝癌发病人数约36.8万例，死亡人数约31.7万例。如何延长肝癌患者的生存期是亟待解决的问题。近年来，酪氨酸激酶抑制剂（tyrosine kinase inhibitor，TKI）单独或联合免疫检查点抑制剂用于原发性肝癌的治疗获得不错的效果。然而多数研究没有联合经导管动脉化疗栓塞术（transcatheter arterial

chemoembolization，TACE）治疗。我们猜想在TKI药物联合免疫检查点抑制剂的基础上再联合TACE治疗有可能使肝癌患者获益更大。因此，本研究旨在评估TACE联合安罗替尼和信迪利单抗治疗肝癌的近期疗效及安全性。

方法：

本研究是一项单臂Ⅱ期临床试验，已通过宜宾市第三人民医院伦理委员会的审查（伦理批号：2022009）。纳入标准：① 年龄18~70岁；② 经临床诊断或组织学检查证实的原发性肝癌；③ 美国东部肿瘤协作组（Eastern Cooperative Oncology Group，ECOG）评分为0~1分；④ 中国肝癌的分期方案（China Liver Cancer Staging，CNLC）Ⅱb~Ⅲb期；⑤ 心肺功能良好；⑥ Child-Pugh分级为8分及以下；⑦ 至少有1个可以通过改进的实体瘤疗效评价标准（modified Response Evaluation Criteria in Solid Tumors，mRECIST）1.1测量的肿瘤病灶。2021年11月1日—2024年3月1日，共纳入61例患者，符合条件者39例。首先对所有入组患者进行TACE治疗。初次TACE术后1周左右予以口服安罗替尼12 mg（根据耐受情况调整用药剂量），第1~14天，每3周1次；同时予以静脉注射信迪利单抗200 mg，第1天，每3周1次。每完成2个周期治疗后根据mRECIST1.1进行疗效评估。研究的主要观察指标为客观缓解率（objective response rate，ORR），次要观察指标为中位无进展生存期（median progression-free survival，mPFS）、疾病控制率（disease control rate，DCR）及安全性。

结果：

ORR为76.9%，DCR为94.9%，mPFS为9.2个月（95% CI：2.317~16.083）。39例（100%）发生1~2级不良反应，15例（38.5%）发生3级不良反应，5例（12.8%）发生4级不良反应，1例患者因上消化道出血死亡。在以TACE联合靶免治疗为主的阶段中，3~4级不良反应的发生率要高于安罗替尼联合信迪利单抗为主的治疗阶段。绝大多数不良反应通过常规治疗手段可缓解。

结论：

TACE联合安罗替尼及信迪利单抗治疗CNLC Ⅱb~Ⅲb期肝癌的疗效确切，总体安全可控。这种联合治疗或将为CNLC Ⅱb~Ⅲb期肝癌患者提供新的治疗模式。但这种治疗模式下所引起的疼痛、呕吐、食欲减退、肝功能损伤、上消化道出血等问题需要进一步探索其解决方案。

Abstract

Background and purpose:

China is a country with high incidence rate and mortality of liver cancer. In 2022

there were approximately 368 000 cases of liver cancer and 317 000 deaths in China. Extending the survival period of liver cancer patients is an urgent issue that we need to address. In recent years

tyrosine kinase inhibitor (TKI) alone or in combination with immune checkpoint inhibitors have achieved good results in the treatment of primary liver cancer. However

most studies did not include the combination of transcatheter arterial chemoembolization (TACE) treatment. We speculate that combining TKI drugs with immune checkpoint inhibitors and TACE therapy may provide greater benefits to liver cancer patients. Therefore

this study aimed to evaluate the short-term efficacy and safety of TACE combined with anlo

tinib and sintilimab in the treatment of liver cancer.

Methods:

This study is a single arm phase Ⅱ clinical trial approved by the ethics committee of The Third People’s Hospital of Yibin (ethical approval numbers: 2022009). Inclusion criteria: ① Age 18-70 years; ② Primary liver cancer confirmed by clinical diagnosis or histopathology; ③ Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1; ④ China Liver Cancer Staging (CNLC) stage Ⅱb-Ⅲb; ⑤ Adequate cardiopulmonary function; ⑥ Child-Pugh score ≤8 points; ⑦ At least one measurable tumor lesion according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) version 1.1. From November 1

2021 to March 1

2024

we recruited 61 patients

of whom 39 met the criteria. Firstly

all enrolled patients received TACE treatment. Approximately one week after the initial TACE procedure

12 mg of anlotinib (adjusted according to tolerance) was administered orally on days 1-14

every 3 weeks; Simultaneously 200 mg of sintilimab was administered intravenously on day 1

every 3 weeks. After completing 2 cycles of treatment

efficacy evaluation was conducted according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) 1.1. The primary observation indicators of the study were objective response rate (ORR)

and the secondary observation indicators were median progression-free survival (mPFS)

disease control rate (DCR) and safety.

Results:

The ORR of this study was 76.9%

DCR was 94.9%

and mPFS was 9.2 months (95% CI: 2.317-16.083). 39 cases (100%) had grade 1-2 adverse reactions

15 cases (38.5%) had grade 3 adverse reactions

5 cases (12.8%) had grade 4 adverse reactions

and 1 patient died due to upper gastrointestinal bleeding. In the stage mainly treated with TACE combined with TKI and immunotherapy

the incidence of grade 3-4 adverse reactions was higher compared with the stage mainly treated with anlotinib combined with sintilimab. The vast majority of adverse reactions can be recovered through

conventional treatment methods.

Conclusion:

TACE combined with anlotinib and sintilimab has a definite therapeutic effect and overall safety and controllability in the treatment of CNLC stage Ⅱb-Ⅲb liver cancer. This combination therapy may provide a new treatment model for CNLC stage Ⅱb-Ⅲb liver cancer patients. However

further exploration is needed to address the pain

vomiting

decreased appetite

liver function damage

upper gastrointestinal bleeding

and other issues caused by this treatment mode.

关键词

Keywords

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