肝动脉灌注化疗联合PD-1抑制剂和酪氨酸激酶抑制剂治疗不可切除肝细胞癌：一家三级医疗中心的经验

Hepatic arterial infusion chemotherapy combined with PD-1 inhibitors and tyrosine kinase inhibitors for unresectable hepatocellular carcinoma: A tertiary medical center experience.

作者信息

Luo Laihui, Xiao Yongqiang, Zhu Guoqing, Huang Aihong, Song Shengjiang, Wang Tao, Ge Xian, Xie Jin, Deng Wei, Hu Zhigao, Wen Wu, Mei Haoran, Wan Renhua, Shan Renfeng

机构信息

Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, China.

Department of Infectious Disease, The First Affiliated Hospital of Nanchang University, Nanchang, China.

出版信息

Front Oncol. 2022 Sep 23;12:1004652. doi: 10.3389/fonc.2022.1004652. eCollection 2022.

BACKGROUND

Unresectable hepatocellular carcinoma (u-HCC) still accounts for the majority of newly diagnosed HCC which with poor prognosis. In the era of systemic therapy, combination therapy with programmed cell death protein-1 (PD-1) inhibitors and tyrosine kinase inhibitors (TKIs) has become mainstream. Hepatic arterial infusion chemotherapy (HAIC) as a local treatment has also shown a strong anti-tumor effect. This study aimed to investigate the efficacy and safety of HAIC, PD-1 inhibitors plus TKIs for u-HCC.

METHODS

This retrospective study included patients with initially u-HCC between October 2020 to April 2022 who had received at least one cycle of therapy with HAIC, PD-1 inhibitors plus TKIs. The primary outcome included overall response rate (ORR), the disease control rate (DCR), surgical conversion rate, progression-free survival (PFS) and treatment-related adverse events.

RESULTS

A total of 145 patients were included in the study. The median treatment cycle of HAIC and PD-1 inhibitors were 3 and 4, respectively. According to the modified RECIST criteria, the best ORR was 57.2% (83/145), 9 had achieved complete response (CR), DCR was 89.7% (130/145). Median time to achieve CR or PR was 65 days. Surgical conversion rate was 18.6% (27/145), seven patients (7/27,25.9%) achieved pathological complete response (pCR). The median follow-up was 12.5 months (4.5-20 months), and the median PFS was 9.7 months. Subgroup analysis showed that Child-pugh A patients had higher DCR (92.2% vs 79.3%, =0.041) than Child-pugh B patients, as well as increased successful conversion rate (22.4% vs 3.4%, =0.019). Patients without vascular invasion and extrahepatic metastases showed higher PR (63.4% vs 43.3%, <0.05) and ORR (73.2% vs 50.0%, <0.05) than those with vascular invasion. The ORR (73.2% vs 45.5%, <0.05) and DCR (95.1% vs 78.8%, <0.05) were also significantly better than those of patients with extrahepatic metastases. HAIC regimen was not related to efficacy (All >0.05). The incidence rate of grade 3/4 treatment-related AEs was 17.7% without fatal events.

CONCLUSION

The triple combination therapy of HAIC and PD-1 inhibitors plus TKIs for patients with initially unresectable HCC exhibited satisfactory efficacy with tolerable toxicity.

背景

不可切除肝细胞癌（u-HCC）仍占新诊断HCC的大多数，预后较差。在全身治疗时代，程序性细胞死亡蛋白-1（PD-1）抑制剂与酪氨酸激酶抑制剂（TKIs）联合治疗已成为主流。肝动脉灌注化疗（HAIC）作为一种局部治疗方法也显示出强大的抗肿瘤作用。本研究旨在探讨HAIC、PD-1抑制剂联合TKIs治疗u-HCC的疗效和安全性。

方法

本回顾性研究纳入了2020年10月至2022年4月期间初诊为u-HCC且接受过至少一个周期HAIC、PD-1抑制剂联合TKIs治疗的患者。主要结局包括总缓解率（ORR）、疾病控制率（DCR）、手术转化率、无进展生存期（PFS）和治疗相关不良事件。

结果

共纳入145例患者。HAIC和PD-1抑制剂的中位治疗周期分别为3个和4个。根据改良的RECIST标准，最佳ORR为57.2%（83/145），9例达到完全缓解（CR），DCR为89.7%（130/145）。达到CR或PR的中位时间为65天。手术转化率为18.6%（27/145），7例患者（7/27，25.9%）达到病理完全缓解（pCR）。中位随访时间为12.5个月（4.5 - 20个月），中位PFS为9.7个月。亚组分析显示，Child-pugh A级患者的DCR（92.2% vs 79.3%，P = 0.041）高于Child-pugh B级患者，成功转化率也更高（22.4% vs 3.4%，P = 0.019）。无血管侵犯和肝外转移的患者比有血管侵犯的患者显示出更高的PR（63.4% vs 43.3%，P < 0.05）和ORR（73.2% vs 50.0%，P < 0.05）。ORR（73.2% vs 45.5%，P < 0.05）和DCR（95.1% vs 78.8%，P < 0.05）也显著优于有肝外转移的患者。HAIC方案与疗效无关（所有P > 0.05）。3/4级治疗相关不良事件的发生率为17.7%，无致命事件。