The Impact of Sorafenib in Combination with Transarterial Chemoembolization on the Outcomes of Intermediate-Stage Hepatocellular Carcinoma

Abstract

Background:We investigated the treatment outcomes and hepatic reserve of transarterial chemoembolization (TACE)-refractory patients with recurrent advanced hepatocellular carcinoma (HCC) treated with TACE plus sorafenib. Methods: Forty-one patients with intermediate-stage HCC defined as being TACE refractory on imaging were treated with sorafenib and TACE between 2009 and 2012 and comprised the combination treatment group. Twenty-nine patients who received repeated TACE after becoming refractory to TACE between 2005 and 2008 comprised the TACE continuation group. Results: Although the interval between successive rounds of TACE was significantly shorter before the patients developed TACE refractoriness, it was significantly longer after the development of TACE refractoriness, in the combination treatment group compared with the TACE continuation group. The appearance of extrahepatic spread and/or vascular invasion differed significantly between the two groups. The median overall survival was significantly longer in the combination treatment group than in the TACE continuation group (20.5 vs. 15.4 months, respectively; hazard ratio = 2.04; 95% confidence interval = 1.20-3.48). The 3-year overall survival rate was 33.4% in the combination treatment group and 3.5% in the TACE continuation group. Downstaging of the Child-Pugh class was significantly less frequent in the combination treatment group than in the TACE continuation group. In COX proportional hazards analyses, sorafenib plus TACE resulted in a better prognosis compared with repeated TACE. Conclusions: Treatment with sorafenib plus TACE in TACE-refractory patients with intermediate-stage HCC resulted in longer intervals between TACE rounds, better maintenance of hepatic reserve, and significantly longer OS compared with repeated TACE.

Tyrosine-kinase inhibitor combined with iodine-125 seed brachytherapy for hepatocellular carcinoma refractory to transarterial chemoembolization: a propensity-matched study

“…Previous studies [ 13 , 14 , 37 ] have reported that HCC patients who received sorafenib after TACE refractoriness had a median OS of 20.5–25.4 months, which seemed longer than that for the patients treated with TKI alone in our study. However, it was noteworthy that these studies only enrolled patients with intermediate-stage disease, who were expected to obtain better outcomes than those included in our study (most of the patients had advanced-stage disease with macrovascular invasion).…”

Recent advances in recurrent hepatocellular carcinoma therapy

“…Treatment with sorafenib and TACE was associated with a higher 5-year OS and PFS compared to those treated with TACE alone in patients with recurrent intermediate-stage HCC and lesions positive for MVI, but patients with MVI-negative lesions did not show a survival benefit from combined therapy[ 114 ]. Treatment with sorafenib plus TACE improves hepatic reserve, leads to a better OS, and results in longer intervals between TACE rounds in TACE-refractory patients with recurrent advanced HCC than repeated TACE treatments[ 115 ]. The RFA plus sorafenib treatment resulted in a significantly improved OS than RFA alone (1-, 3-, and 5-year OS rates of RFA-sorafenib vs RFA: 97.7%, 83.7%, and 54.7% vs 93.1%, 61.3%, and 30.9%, respectively), suggesting that adjuvant sorafenib combined with RFA was superior to RFA alone in improving survival results in patients with recurrent HCC who meet the Milan criteria after initial LT[ 116 ].…”

Subsequent Treatment after Transarterial Chemoembolization Failure/Refractoriness: A Review Based on Published Evidence

“…the transition to post-treatments. 30 Huang et al 31,32 performed two similar studies comparing the treatment outcomes of TACE monotherapy and TACE combined with S-1 chemotherapy. Both studies included 26 patients with intermediate HCC, and TACE failure/refractoriness was defined as disease progression or shrinkage of <25% in hypervascular tumor lesions after 1-2 cycles of TACE.…”