Addition of Immune Checkpoint Inhibitor Showed Better Efficacy for Infiltrative Hepatocellular Carcinoma Receiving Hepatic Arterial Infusion Chemotherapy and Lenvatinib: A Multicenter Retrospective Study

Abstract

Wei Wang,1,* Ruixia Li,2,* Hui Li,3 Murong Wang,3 Juncheng Wang,4 Xiaohui Wang,5 Qunfang Zhou6 1Department of General Surgery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, People’s Republic of China; 2Department of Thyroid Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China; 3Department of Minimally Invasive Interventional Radiology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, People’s Republic of China; 4Department of Liver Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, People’s Republic of China; 5Department of Hepatobiliary Surgery, Hunan Provincial People’s Hospital, Changsha, Hunan, People’s Republic of China; 6Department of Interventional Radiology, Chinese PLA General Hospital, Beijing, 100853, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaohui Wang, Department of Hepatobiliary Surgery, Hunan Provincial People’s Hospital, Changsha, Hunan Province, 410005, People’s Republic of China, Tel [phone], Email [email protected] Qunfang Zhou, Department of Interventional Radiology, Chinese PLA General Hospital, Beijing, 100853, People’s Republic of China, Tel [phone], Email [email protected]: The prognosis of infiltrative hepatocellular carcinoma (HCC) is dismal. Hepatic arterial infusion chemotherapy (HAIC) plus Lenvatinib (Len) and immune checkpoint inhibitor (ICI) have shown promising results for HCC. However, this three combination therapy on infiltrative HCC is unknown. In this study, we compared HAIC plus lenvatinib (Len) and programmed cell death protein-1 (PD-1) inhibitor with HAIC plus Len for infiltrative HCC.Patients and Methods: This multi-center cohort study included patients with infiltrative HCC who received HAIC combined with Len (HAIC+Len group, n = 173) or HAIC combined with Len and PD-1 inhibitor (HAIC+Len+ICI group, n = 128) as the first-line treatment from January 2019 to December 2021. To balance any intergroup differences, one-to-one propensity score matching (PSM) was applied. Overall survival (OS) and progression-free survival (PFS) were compared between the two groups.Results: After PSM, the median OS was 14.1 ± 1.0 and 16.1 ± 1.4 months in the HAIC+Len and HAIC+Len+ICI groups, respectively. The median PFS was 4.6 ± 0.4 months in the HAIC+Len group and 7.5 ± 0.8 months in the HAIC+Len+ICI group. The HAIC+Len+ICI group showed significantly better OS (hazard ratio [HR], 0.66; 95% CI, 0.49– 0.90; P = 0.008) and PFS (HR, 0.53; 95% confident index [CI], 0.40– 0.70; P < 0.001) compared with the HAIC+Len group. Subgroup analysis revealed that for OS in HCC without metastasis, the addition of PD-1 inhibitor was not significant (HR, 0.68; 95% CI, 0.43– 1.07; P = 0.091). No difference was observed in OS between low (2– 3 cycles) and high (4– 6 cycles) level of HAIC cycles (HR, 0.99; 95% CI, 0.67– 1.44; P = 0.938).Conclusion: The HAIC+Len+ICI group had a longer PFS and OS compared with the HAIC+Len group, demonstrating an acceptable safety profile. This triple combination strategy may be an alternative treatment for infiltrative HCC management.Plain language summary: The evidence of HAIC plus Len and PD-1 inhibitors for infiltrative HCC is limited. There was no study to evaluate the efficacy of HAIC combined with Len and PD-1 inhibitors for infiltrative HCC. In this study, we found that HAIC plus Len and PD-1 inhibitor (HAIC+Len+ICI) was associated with longer progression-free survival and overall survival than HAIC plus Len combination (HAIC+Len) for patient with infiltrative HCC. In addition, OS in patients with metastasis was improved with HAIC+Len+ICI treatment. OS in patients without metastasis, addition of PD-1 inhibitor after HAIC and Len was not beneficial. What’s more, three cycles of HAIC are adequate, especially for patients with high tumor burden, especially with main branch portal vein tumor thrombus (PVTT). Our research provides new evidence that HAIC+Len+ICI treatment significantly improved the OS and PFS of infiltrative HCC patients compared with those who received HAIC+Len treatment. It provides a strong reference for clinical treatment.Keywords: Infiltrative hepatocellular carcinoma, hepatic arterial infusion chemotherapy, Len, PD-1 inhibitor, Prognosis

Keywords

• infiltrative hepatocellular carcinoma
• hepatic arterial infusion chemotherapy
• len
• pd-1 inhibitor
• prognosis