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.