What Is the Most Suitable Agent Combined With Apatinib for Transarterial Chemoembolization Treatment in Advanced Hepatocellular Carcinoma Patients? A Systematic Review and Network Meta-analysis

PURPOSE: Combined therapy with transarterial chemoembolization (TACE) and apatinib is superior in therapeutic effect compared with TACE alone in patients with hepatocellular carcinoma (HCC). To determine the most suitable agent combined with apatinib for TACE treatment, we did a systematic review and network meta-analysis. METHODS: Four electronic databases were searched from inception until November 2021. Randomized controlled trials (RCTs) and retrospective studies that combined therapy of TACE and apatinib (TACE+A) compared with TACE alone were included. We performed random-effect pairwise and network meta-analyses to summarize the outcomes about efficacy and safety. RESULTS: Forty-five original studies including 3,876 patients were included. In terms of efficacy, we evaluated treatment response, 6 months overall survival (OS), 1 year OS, 6 months progression-free survival (PFS), 1 year PFS, alphafetoprotein (AFP), matrix metalloproteinase 9 (MMP9), and vascular endothelial growth factor (VEGF). Significant differences always appear in TACE agent subgroups of adriamycin, platinum, and fluorouracil from both pairwise and network meta-analysis, while significant differences could also be found in apatinib dosage of 500 and >500 mg/day subgroups and in both RCT and retrospective study subgroups. From second time network analysis, compared with TACE alone, subgroups with TACE agents of oxaliplatin, cisplatin, pirarubicin, epirubicin, and 5-fluorouracil ranked front. In addition, the safety of adriamycin, platinum, and fluorouracil subgroups is acceptable. CONCLUSIONS: In conclusion, the most suitable agents in TACE combined with apatinib were adriamycin+platinum ± fluorouracil combination therapy. SYSTEMATIC REVIEW REGISTRATION: The study was registered with https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=311650, PROSPERO, CRD4202022311650