Song Chen,1,* Ning Wang,2,* Yi Xiao,3,* Xiongying Jiang,4,* Feng Shi,5 Hongjie Cai,1 Shuangyan Tang,6 Wenbo Guo,1 Wenquan Zhuang1 

1Department of Interventional Radiology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China; 2Department of Radiology, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China; 3Center of Hepato-Pancreato-Biliary Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China; 4Interventional Radiology Division, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 5Department of Interventional Radiology, Guangdong Provincial People’s Hospital, Guangzhou, People’s Republic of China; 6Department of Radiology, the Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Wenbo Guo, Department of Interventional Radiology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China, Email guowenbo@mail.sysu.edu.cn Wenquan Zhuang, Department of Interventional Radiology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China, Email zhuangwq@mail.sysu.edu.cn

Purpose: This study aimed to evaluate the clinical efficiency and safety of hepatic arterial infusion chemotherapy (HAIC) combined with lenvatinib and programmed cell death protein-1 (PD-1) inhibitor for patients with hepatocellular carcinoma (HCC) and lung metastasis.
Methods: In this multicenter retrospective study, treatment-naive patients with advanced (BCLC stage C) HCC and lung metastases who received lenvatinib and PD-1 inhibitor - with or without HAIC - between January 2019 and January 2024 were reviewed. Propensity score matching (PSM) was applied to balance baseline characteristics between the two groups. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) according to RECIST 1.1 criteria, as well as adverse events (AEs).
Results: A total of 422 eligible patients were included, with 169 receiving HAIC (HLP group) and 253 receiving lenvatinib plus PD-1 inhibitor (LP group). After 1:1 PSM, 151 patients were matched in each group. The HLP group demonstrated significantly longer median OS compared to the LP group (26.0 versus 8.4 months; hazard ratio [HR]: 0.36; 95% confidence interval [CI]: 0.27– 0.49; P < 0.001). Median PFS was also improved in the HLP group (7.6 versus 5.5 months; HR: 0.77; 95% CI: 0.59– 1.00; P = 0.048). ORR and DCR were significantly higher in the HLP group (ORR: 47.7% versus 20.5%, P < 0.001; DCR: 86.1% versus 72.2%, P = 0.003). Although the HLP group experienced a higher incidence of both all-grade and grade 3/4 AEs, all were manageable, and no grade 5 events occurred.
Conclusion: HAIC combined with lenvatinib and PD-1 inhibitor shows promise as a treatment for advanced HCC with lung metastases, offering improved prognosis and a manageable safety profile.

Keywords: hepatocellular carcinoma, hepatic arterial infusion chemotherapy, lenvatinib, programmed cell death protein-1 inhibitor, propensity score matching