TACE 2: A randomized placebo-controlled, double-blinded, phase III trial of sorafenib in combination with transarterial chemoembolisation (TACE) in patients with unresectable hepatocellular carcinoma
Session type: Oral
TACE is the standard-of-care for patients with intermediate stage HCC while sorafenib (S) is the current standard for advanced disease. TACE 2 was designed to determine whether TACE + S improves progression free survival (PFS) compared to TACE alone
Patients were randomised 1:1 to continuous S (400mg BD) or placebo (P). Inclusion criteria included; unresectable HCC, ECOG PS ≤1 and Child Pugh A liver score. Study-drug was commenced at randomisation and TACE performed at 2-5 weeks using drug eluting beads (DEB) loaded with 150mg doxorubicin. Further TACE was performed on demand. Primary outcome measure (OM) was PFS. Secondary OM included overall survival (OS), response rate and safety. Target recruitment was 412 to detect a (Hazard Ratio) HR of 0.72 with 2-sided significance α=0.05 and 85% power. A planned interim futility analysis (IFA) was performed at 45% of trial events.
At the IFA, 294 had been randomised from 20 UK sites. Median age 67 yrs, 169 (58%) PS 0. In 229 cirrhotic patients, liver disease was: 43% alcohol, 24% HCV; 13% HBV; 38% other. Median PFS for the S and P group was 7.8 (95% CI 5.9, 10.0) and 7.7 (95% CI 5.9, 10.5) months; (HR) of 1.03 (95% CI 0.75, 1.42 p=0.85). For the S and P groups: median OS was 18.8 (95% CI 12.3, 24.0) and 19.6 (95% CI 14.8, 24.0) months; there were 77 and 78 SAEs; 195 and 256 TACE procedures. Median duration of S and P was 5.9 and 7.7 months; median of patient average daily dose was 649mg and 800mg.
The TACE 2 trial provides no evidence that addition of S to DEB-TACE improves PFS or OS in European patients with intermediate HCC. Alternative systemic therapies need to be evaluated in combination with TACE to improve outcomes for this patient population.