Sorafenib plus hepatic arterial infusion chemotherapy versus sorafenib plus transarterial chemoembolization in advanced hepatocellular carcinoma: a phase III trial and biomarker analyses.

OBJECTIVE: Although sorafenib plus transcatheter arterial chemoembolization (SoraTACE) has been widely applied for advanced hepatocellular carcinoma (HCC) in most Asian countries, sorafenib plus hepatic arterial infusion chemotherapy (SoraHAIC) may be a better alternative. This phase III trial assessed the efficacy and safety of SoraHAIC versus SoraTACE in patients with advanced HCC. METHODS: Participants were randomly assigned (2:1) to receive SoraHAIC (400 mg of sorafenib twice daily plus FOLFOX-HAIC every 3 weeks) or SoraTACE (400 mg of sorafenib plus TACE). The primary endpoint was overall survival (OS). RESULTS: From August 2016 to October 2020, 207 participants were allocated to receive SoraHAIC (n = 141) or SoraTACE (n = 66). SoraHAIC significantly improved OS (median OS, 15.7 vs. 11.2 months; hazard ratio [HR], 0.58 [95% CI: 0.42, 0.80]; P < 0.001) and progression-free survival (median, 7.2 vs. 4.1 months; HR, 0.48 [95% CI: 0.35, 0.65]; P < 0.001) compared to SoraTACE. The incidence of grade 3-4 treatment-related adverse events was significantly lower with SoraHAIC (39.3%) than SoraTACE (56.7%) (P < 0.023). Biomarker exploration indicated that patients with higher phosphofructokinase (PFKM) expression benefitted more from SoraTACE. CONCLUSIONS: SoraHAIC significantly improves OS over SoraTACE in participants with advanced HCC. Participants with high PFKM expression might benefit more from SoraTACE.