Table 1. Randomized phase II, phase III clinical trials of combination therapy with TACE ± sorafenib in unresectable HCC.

Trial name	Number of patients and trial design	Primary end point	Timing of sorafenib	Duration of Sor (weeks)/daily dose of Sor (mg) (median)	TACE session	HFSR (any grade (%)/permanent discontinuation (%) due to AE	ORRs	Results
Post TACE (Double blind), Kudo et al. (12)	Sor n=229 (400 mg twice daily) vs. Plb n=229; PS-1: 12%	TTP (recurrence after CR, or ≥25% tumor size or new lesion after PR)	After (P/C) response to conventional TACE	17 weeks/385 mg	(Prior TACE) one: 65%, two: 35%	82%/45%	(prior TACE) CR: 62%, PR: 38%	Negative
SPACE (Double blind), Lencioni et al. (13)	Sor n=154 (400 mg twice daily) vs. Plb n=153; BCLC B	TTP (according to mRECIST criteria)	On day 1 (4-week cycle) + DEB-TACE on C1, C3, C7, C13	21 weeks/566 mg	One: 36%, two: 35%, >two: 26% vs. one: 19%, two: 38%, >two: 40%	46%/27%	55.9% vs. 41.3%	Negative
TACE-2 (Double blind), Meyer et al. (14)	Sor n=157 (400 mg twice daily) vs. Plb n=156; PS-1: 37%	PFS (progression: RECIST v1.1; or death)	On day 1 + DEB-TACE	17 weeks/660 mg	One: 41%, Two: 26%, >two: 22% vs. one: 28%, two: 35%, >two: 29%	42%/19%	54% vs. 52%	Negative
TACTICS, Kudo et al. (15)	Sor n=80 (400 mg/day) vs. Plb n=76; BCLC A: 38%, PS-1: 12%	PFS (progression: [unTACEable criteria or TACE failure/refractoriness criteria (JSH); or death]	2–3 weeks prior to first conventional TACE	38.7 weeks/355 mg	–	53.2%/2.5%	71.3% vs. 61.8%	Positive

Sor, sorafenib; TACE, transarterial chemoembolization; HCC, hepatocellular carcinoma; HFSR, hand-foot skin reaction; AE, adverse events; ORR, overall response rate; Plb, placebo; PS, performance status; TTP, time to progression; CR, complete response; mRECIST, modified Response Evaluation Criteria in Solid Tumors; DEB-TACE, drug-eluting beads TACE; PFS, progression free survival; JSH, Japan Society of Hepatology.