Efficacy and Safety of HAIC-FOLFOX Plus Tyrosine Kinase Inhibitors and Immune Checkpoint Inhibitors as First-line Treatment for Unresectable Advanced Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis
Peng Jiang, Chao Chen, Jing Tian, Fan Yang, Zhenyu Jiang, Anxiang Hu, Bin Liu
Abstract
BACKGROUND: Advanced hepatocellular carcinoma (HCC) has been treated with targeted therapy, immunotherapy, or a combination of both, however, the overall clinical efficacy is still unsatisfactory. Hepatic arterial infusion chemotherapy (HAIC), as a localized treatment modality, has demonstrated favorable therapeutic efficacy in patients with advanced HCC accompanied by portal vein tumor thrombus and extensive intrahepatic metastasis. In recent years, the combination of HAIC with immune and targeted therapy has gradually gained acceptance in East Asian countries. However, further investigation is necessary to assess the efficacy and safety of this triple therapy. METHOD: PubMed, Embase, the Cochrane Library, and Web of Science databases were systematically searched for studies conducted within the past 5 years on HAIC combined with immunotherapy and targeted therapy as first-line treatment for advanced HCC. According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted this meta-analysis. Additionally, the quality of included studies was assessed using the Joanna Briggs Institute (JBI) scale. Outcomes such as overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs)were extracted and pooled from eligible studies. RESULT: = 76.9%, P = 0.000). In terms of safety, the incidence rates of any grade AEs, ranked from high to low, were as follows: aminotransferase increased (61.3%), nausea and vomiting (40.5%), hypertension (37.8%), thrombocytopenia (37.4%), hyperbilirubinemia (36.7%), abdominal pain (35.6%), leukopenia (34.6%), hypothyroidism (19.0%), rash (14.4%). Grade 3-4 AEs ranked from high to low were as follows: aminotransferase increased (10.8%), thrombocytopenia (7.9%), hypertension (7.4%), leukopenia (5.0%). No treatment-related deaths occurred, patients receiving this triple therapy demonstrated favorable tolerability. CONCLUSION: The combination of hepatic arterial infusion chemotherapy with tyrosine kinase inhibitors and immune checkpoint inhibitors as a first-line therapy for unresectable advanced HCC demonstrates promising therapeutic efficacy and favorable safety.