Efficacy of Local‐regional Treatment Plus Sorafenib in Intermediate‐stage Hepatocellular Carcinoma Patients Refractory to Transarterial Chemoembolization

Sorafenib treatment is suggested for patients with intermediate-stage hepatocellular carcinoma (HCC) refractory to transarterial chemoembolization (TACE). This study aimed to study if combining local-regional treatment with sorafenib adds benefit to patients who had tumor progression after three sessions of TACE within 12 months. We retrospectively analyzed the treatment outcomes of sorafenib alone and combined treatment of sorafenib and local-regional therapies in intermediate-stage HCC patients after using inverse probability of treatment weighting (IPTW). Forty-nine patients were enrolled; 28 patients were treated with sorafenib alone, whereas 21 patients received TACE or radiofrequency ablation (RFA) in addition to sorafenib. After IPTW, the two groups were well-balanced for most baseline characteristics. The overall response rate (ORR) and disease control rate (DCR) were significantly higher in the sorafenib-combination group than the sorafenibalone group (ORR: 41.3% vs 10.0%, P = .001; DCR: 44.6% vs 22.1%). The PFS was also significantly longer in the patients of the sorafenibcombination group than the alone group (median 5.3 vs 3.0 months, HR, 0.55; 95% CI, 0.35-0.88). The risk of extrahepatic metastases was significantly lower in the sorafenib-combination group (HR, 0.04; 95% CI, 0.01-0.50). The incidence of adverse events was comparable between sorafenib-combination and sorafenib-alone groups. Loco-regional therapy may be still able to exert additional survival benefit to patients taking sorafenib for TACE-refractory intermediate-stage HCC showing a better PFS and lower risk of extrahepatic metastases without causing significant liver dysfunction. Further investigations to identify patients who will be more likely to benefit from the combination of sorafenib with local-regional therapy are needed.