Sorafenib with versus without Concurrent ConventionalTransarterial Chemoembolization (cTACE) in Patients Advanced Hepatocellular Carcinoma (HCC): Results from a Multicenter, Open-Label, Randomized, Controlled Phase III STAH Trial

Abstract

Background and Aims: Sorafenib is the standard first-line therapy for patients (pts) with advanced HCC (aHCC). cTACE is an effective treatment for unresectable HCC. A previous phase II study revealed that sorafenib combined with concurrent cTACE (SOR+T) tended to improve outcomes. Herein, we present the results from an investi-stage, extent of vascular invasion, Child-Pugh score and serum alpha fetoprotein level. All eligible pts received 800 mg sorafenib within 3 days (Arm S and C) and cTACE within 7-21 days after randomization, and repeating cTACE on demand (Arm C). The study continued until progression or unacceptable toxicities were observed. The primary endpoint was overall survival (OS), and secondary endpoints included time to progression (TTP), progression-free survival (PFS), tumor response rate (TRR), and safety profile. Results: Between January 2013 and December 2015, 339 pts were enrolled from 13 hospitals in South Korea, and the last pt com- pleted the trial on June 2017. Pts baseline characteristics were well balanced. For Arm C and S, respectively, median OS was 12.8 vs. 10.8 months (m) (hazard ratio [HR], 0.91; 95% confidence interval [CI] 0.69 – 1.21; p = 0.290); median TTP was 5.3 vs. 3.5 m (HR, 0.67; 95% CI, 0.53 – 0.85; p = 0.003); median PFS was 5.2 vs. 3.6 m (HR, 0.73; 95% CI, 0.59 – 0.91; p = 0.01); TRR was 60.6% vs. 47.3% (p = 0.005). For Arm C and S, respectively, serious adverse events (AE) were 33.3% vs. 19.8% (p = 0.006), and grade ≥ 3 AE were increased alanine aminotransferase (20.3% vs. 3.6%), hyperbilirubinemia (11.8% vs. 3.0%), ascites (11.8% vs. 4.2%), thrombocytopenia (7.2% vs. 1.2%), anorexia (7.2% vs. 1.2%), hyponatremia (5.2% vs. 0%) (p < 0.05); hand- foot skin reaction (10.5% vs. 11.4%), encephalopathy (5.2% vs. 1.2%) and diarrhea (5.2% vs. 4.2%). Subgroup analysis showed a survival benefit in pts (46.4%) of Arm C who received ≥ 2 cTACE sessions when compared to pts in Arm S (18.6 vs. 10.8 m; HR, 0.58; 95% CI, 0.40-0.82; p = 0.006). Conclusion: SOR+T therapy did not improve OS versus sorafenib alone in pts with aHCC. However, SOR+T therapy significantly improved TTP, PFS, and TRR, and a survival benefit was observed in the pts who received SOR+T ≥ 2 cTACE sessions.

gator-initiated phase III trial that evaluated the effects of SOR+T in pts with aHCC. Method: Pts were randomly assigned (1:1) into one of two arms, to receive sorafenib with cTACE (Arm C) or without cTACE (Arm S) according to modified International Union Against Cancer tumor