Recent advances in multidisciplinary management of hepatocellular carcinoma

Table 1 Phase III trials of some systemic targeted agents in advanced hepatocellular carcinoma

Ref.	Study design	Patients, n	Overall survival, mo
Zhu et al[109] (SEARCH trial)	Sorafenib vs sorafenib + erlotinib	358 vs 362	Sorafenib: 8.5 Sorafenib + erlotinib: 9.5
Cheng et al[105] (SUN1170 trial)	Sorafenib vs sunitinib	544 vs 530	Sorafenib: 10.2 Sunitinib: 7.9
Cainap et al[106] (LIGHT trial)	Sorafenib vs linifanib	517 vs 518	Sorafenib: 9.8 Linifanib: 9.1
Johnson et al[107] (BRISK-FL trial)	Sorafenib vs brivanib	578 vs 577	Sorafenib: 9.9 Brivanib: 9.5
Llovet et al[108] (BRISK-PS trial)	Brivanib vs placebo	263 vs 132	Brivanib: 9.4 Placebo: 8.3

Table 2 Clinical studies on combined sorafenib and transcatheter arterial chemoembolization for intermediate and advanced hepatocellular carcinoma

Ref.	Study design	Timing of sorafenib	Patients, n	BCLC stage	Child-Pugh class	Primary endpoint results
Kudo et al[155]	Sorafenib + TACE vs TACE	Sequential	229 vs 229	B	A	TTP (5.4 mo vs 3.7 mo)
Lencioni et al[151] (SPACE trial)	Sorafenib + DEB-TACE vs DEB-TACE + placebo	Continuous	154 vs 153	B	A	TTP (169 d vs 166 d; P = 0.072)
Martin et al[158]	Sorafenib + DEB-TACE vs DEB-TACE	NR	30 vs 120	B, C	B	OS (12 mo vs 10 mo)
Sansonno et al[154]	Sorafenib + TACE vs TACE	Sequential	40 vs 40	B	A	TTP (9.2 mo vs 4.9 mo)
Han et al[156] (subgroup analysis of START)	Sorafenib + TACE	Sequential	63	A, B, C	A	TTP (10.6 mo) OS (16.5 mo)
Chung et al[150] (subgroup analysis of START)	Sorafenib + TACE	Sequential	63	A, B, C	A	DCR (52%)
Park et al[149] (COTSUN Korea)	Sorafenib + TACE	Interrupted	50	B, C	A, B	TTP (7.1 mo) PFS (52% at 6 mo)
Pawlik et al[148]	Sorafenib + DEB-TACE	Continuous	35	B, C	A, B	DCR (95%) OR (58%)
Cabrera et al[153]	Sorafenib + DEB-TACE or Y-90	Continuous	47	B, C	A, B	At 6 mo DCR (68%) OS (8.5 mo)

BCLC: Barcelona clinic liver cancer; TACE: Transcatheter arterial chemoembolization; DBE: Drug-eluting beads; NR: Not recorded; TTP: Time to progression; DCR: Disease control rate; OR: Objective response; OS: Overall survival; PFS: Progression-free survival.

Table 3 Combined sorafenib plus systemic anticancer therapy for unresectable hepatocellular carcinoma

Ref.	Chemotherapeutic agent	Type of study	Patients, n	Median OS, mo	DCR, %	Median PFS, mo
Abou-Alfa et al[160]	Doxorubicin	Multicenter randomized prospective phase II	47 vs 49	13.7 vs 6.5	62	6.0 vs 2.7
Hsu et al[166]	Tegafur/uracil	Prospective phase II	53	7.4	57	3.7
Prete et al[161]	Long-acting octreotide	Prospective phase II	50	12	76	7
Abou-Alfa et al[165]	PR-104	Prospective phase I	14	NR	50	NR
Lee et al[164]	S-1 fluoropyrimidines	Prospective phase I	20	10.4	52.9	3.9
Petrini et al[163]	5-Fluorouracil	Prospective phase II	39	13.7	48.7	7.5