Tim Meyer, MBBS
As reported in The Lancet Gastroenterology & Hepatology by Tim Meyer, MBBS, of the University College London, and colleagues, the UK phase III TACE 2 trial has shown no progression-free survival benefit with the addition of sorafenib (Nexavar) to transarterial chemoembolization in patients with unresectable hepatocellular carcinoma. The trial was terminated early for futility.
In the double-blind study, 313 patients with liver-confined disease from 20 UK sites were randomized between November 2010 and December 2015 to receive transarterial chemoembolization with drug-eluting beads and either sorafenib at 400 mg twice daily (n = 157) or placebo (n = 56). The primary endpoint was progression-free survival in the intent-to-treat population.
Survival and Toxicity
Formal interim futility analysis in July 2015 indicated a hazard ratio (HR) of 1.03 (P = .85), resulting in early trial closure. Median follow-up was 620 days.
Median progression-free survival was 238 days in the sorafenib group vs 235 in the placebo group (HR = 0.99, P = .94). Median overall survival was 631 vs 598 days (HR = 0.91, P = .57). Overall response rates were 36% vs 31% on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and 54% vs 52% on modified RECIST.
The most common grade 3 or 4 adverse events in the sorafenib group were fatigue (18% vs 13%), abdominal pain (13% vs 8%), diarrhea (10% vs 3%), gastrointestinal disorders (11% vs 8%), and hand-foot skin reaction (8% vs 0%). Serious adverse events occurred in 41% vs 32% of patients.
The investigators concluded: “The addition of sorafenib to [drug-eluting bead]-[transarterial chemoembolization] does not improve progression-free survival in European patients with hepatocellular carcinoma. Alternative systemic therapies need to be assessed in combination with [transarterial chemoembolization] to improve patient outcomes.” ■