Efficacy and safety of hepatic arterial infusion chemotherapy combined with immune checkpoint inhibitors and tyrosine kinase inhibitors in advanced hepatocellular carcinoma: A systematic review and meta‑analysis

Abstract

At present, hepatic arterial infusion chemotherapy (HAIC) for the treatment of hepatocellular carcinoma (HCC) is often applied to patients who are not suitable or are unwilling to undergo surgical treatment. However, to the best of our knowledge, the efficacy and safety of HAIC combined with immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) in HCC have not been fully demonstrated. Published studies involving the treatment of patients with HCC with HAIC, ICIs and TKIs were searched from public databases, including PubMed, Embase, the Cochrane Library and Sinomed. Efficacy and safety data for each study, including progression-free survival (PFS), overall survival (OS) and adverse events (AEs) were collected. The present study included 17 treatment groups from 15 studies, including 1,987 patients with HCC in the systematic review. The target population was dominated by those unsuitable for surgical treatment, with Barcelona Clinic Liver Cancer stage B or C, Eastern Cooperative Oncology Group performance status ≤2 and Child-Pugh score A or B. The results showed that the longest estimated median PFS (95% CI) in the HAIC + ICI/TKI therapy group (group C) was 9.37 months (95% CI, 6.81-11.93); in the HAIC therapy group (group B) was 7.45 months (95% CI, 6.45-8.46); and in the ICIs + other systemic therapies group (group A) was 5.92 months (95% CI, 5.31-6.54). There was no significant difference in the expected OS among the three groups, which may be because OS events were not reached in numerous studies during the follow-up time. The incidence of treatment-related adverse effects, such as increased AST [14/221 (6.33%)], increased ALT [13/221 (5.88%)], and decreased platelet count [13/221 (5.88%)], was not significantly increased in group C when compared with groups A or B (P>0.05). In conclusion, the effectiveness of HAIC + ICI/TKI for the treatment of advanced HCC was better than that of ICIs + other systemic therapies or HAIC alone. In addition, the incidence of AEs above grade 3 was not significantly higher compared with that in the other treatment groups, and the safety profile was good.

Keywords: adverse events; hepatic arterial infusion chemotherapy; hepatocellular carcinoma; immune checkpoint inhibitors; tyrosine kinase inhibitors.