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

Masaki Kaibori,Shuji Kariya,Hideyuki Matsushima,Kousuke Matsui,Hisashi Kosaka,Kengo Yoshii,Morihiko Ishizaki,Mitsugu Sekimoto

doi:10.31557/apjcp.2021.22.4.1217

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.

Highlights

Hepatocellular carcinoma (HCC) is the fifth and eighth most common malignancy in men and women, respectively, and more than 500,000 new cases are diagnosed worldwide each year (Bosch et al, 1999; Bosch et al, 2004; Arzumanyan et al, 2013)
The median overall survival (OS) was significantly longer in the combination treatment group than in the transarterial chemoembolization (TACE) continuation group (20.5 vs. 15.4 months, respectively; hazard ratio (HR) = 2.04; 95% confidence interval (CI) = 1.20–3.48; p = 0.009; Figure 1c)
In clinical guidelines such as those proposed by the Barcelona Clinic Liver Cancer (BCLC), Association for the Study of Liver Diseases (AASLD), APASL, and Japan Society of Hepatology (JSH), TACE is recommended as a standard treatment for intermediate-stage hepatocellular carcinoma (HCC) (Bruix et al, 2011; Kudo et al, 2016; Omata et al, 2017; European Association for the Study of the Liver, 2018; Forner et al, 2018; Heimbach et al, 2018)

Summary

Introduction

Hepatocellular carcinoma (HCC) is the fifth and eighth most common malignancy in men and women, respectively, and more than 500,000 new cases are diagnosed worldwide each year (Bosch et al, 1999; Bosch et al, 2004; Arzumanyan et al, 2013). Transarterial chemoembolization (TACE) confers a survival benefit in patients with intermediate-stage HCC (Llovet et al, 2003). It was shown that sorafenib significantly prolongs progression-free survival (PFS) and overall survival (OS) in patients with advanced HCC (Llovet et al, 2008; Cheng et al, 2009). The TACTICS phase II study, which investigated patients with BCLC-A and BCLC-B lesions in Japan, yielded epoch-making results (Kudo et al, 2020). A significantly longer median PFS was observed in the TACE plus sorafenib combination group compared with the TACE only group; the authors are awaiting the OS results. Combination therapy with TACE and sorafenib is expected to improve the prognosis of patients with HCC. We investigated the treatment outcomes and hepatic reserve in TACE-refractory patients with recurrent advanced HCC after treatment with TACE plus sorafenib

Materials and Methods

Methods

Results

Discussion