Table 3. Clinical trials regarding TACE combine with targeted therapy (with published results).

Agents	Stage	patients(n)	Therapeutic scheme	First or second line	Efficacy (combined therapy vs monotherapy)	Adverse events (AEs)	Ref
Sorafenib + TACE	Phase 3	458	Sorafenib 400 (n = 229) mg bid po or placebo (n = 227) po after 1-2 TACE	First line	mTTP: 5.4 vs. 3.7 months 3-months PFR: 65.0% vs 58.7% mOS: 29.7 months vs. NR	HFSR, elevated lipase, alopecia and rash/desquamation.	[16]
Sorafenib + TACE	Phase 2	304	Sorafenib 400 mg bid po (n = 82) + TACE vs TACE alone (n = 222)	First line	mTTP: 6.3 vs 4.3 months mOS: 7.5 vs 5.1 months DCR: 58.5% vs 44.5%	hand-foot skin reaction, alopecia and diarrhea, gastrointestinal bleeding, hyperbilirubinemia and hepatic encephalopathy.	[17]
Sorafenib + TACE	Phase 2	80	Sorafenib 400 (n = 31) mg bid po or placebo (n = 31) po after TACE	First line	mTTP: 9.2 vs. 4.9 months	anorexia, diarrhea, fatigue, hand–foot skin reaction, hematological event, nausea, rash/desquamation.	[18]
Sorafenib + TACE	Phase 2	43	Sorafenib: starting dose of 200 mg bid po increased to 400 mg bid in the majority of patients (n = 13), or placebo (n = 30) after TACE	First line	mOS: 20.6 vs 13.8 months;	pain, nausea, vomiting and mild elevation of liver enzymes.	[19]
Sorafenib + TACE	Phase 2	355	Sorafenib 400mg bid po plus TACE (n = 164) vs sorafenib alone (n = 191)	First line	mTTP: 2.5 vs 2.1 months; mOS: 8.9 vs 5.9 months.	hand-foot skin reaction	[20]
Sorafenib + TACE	Phase 2	45	Sorafenib 200mg bid po plus TACE	First line	mOS: 27 vs. 17 months	hand-foot skin reaction, rash and diarrhea.	[21]
Bevacizumab + TACE	Phase 2	32	Bevacizumab (5 mg/kg) (n = 16) or placebo (n = 16)	First line	mTTP: 7.2 vs. 11.7 months mOS: 5.3 vs 13.7 months	severe bleeding, vascular, and septic events; right heart dilatation, anorexia, fatigue, or alopecia were low-grade events	[22]
Bevacizumab + TACE	Phase 2	30	Bevacizumab 10 mg/kg IV (n = 15) or placebo (n = 15).	First line	mOS: 49 vs. 61 months 16-weeks PFS rate: 79% vs 19%.	elevated transaminases, pain, pyrexia, nausea/vomiting, and fatigue.	[23]
Sunitinib + TACE	Phase 2	103	Sunitinib (n = 38) 37.5 mg po daily or placebo (n = 65) after TACE	First line	mOS: 8.8 vs 6.3 months mTTP: 3.9 vs 2.5 months	hrombocytopenia, fatigue, leukopenia, and anemia. upper gastrointestinal bleeding, hepatic encephalopathy, and hyperbilirubinemia.	[24]
Sunitinib + TACE	Phase 2	16	Sunitinib 37.5 mg po daily after TACE	First line	mPFS: 8 months mOS: 14.9 months DCR: 81%.	thrombocytopenia, increase of amylase/lipase, lymphopenia, and fatigue.	[25]