Progress in systemic therapy of advanced hepatocellular carcinoma

Table 1 Completed randomized phase III clinical trials of targeted drugs in hepatocellular carcinoma (2013-2015)

Drug studied	Main targets	Treatment line	Patients	RR/DCR	TTP (mo)	OS (mo)
Brivanib vs sorafenib (BRISK-FL, NCT00858871)	VEGFR2, FGFR1	1st	Brivanib (n = 577) Sorafenib (n = 578)	12% vs 9%, P = 0.0569 66% vs 65%, P = 0.8739	4.1 vs 4.2; HR = 1.01 (95%CI: 0.88-1.16); P = 0.8	9.5 vs 9.9; HR = 1.05 (95%CI: 0.94-1.23); P = 0.31
Brivanib vs placebo (BRISK-PS, NCT01108705)		2nd	Brivanib (n = 263) Placebo (n = 132)	10% vs 2%, P = 0.003 61% vs 40%, P < 0.001	4.2 vs 2.7; HR = 0.56 (95%CI: 0.42-0.78); P = 0.001	9.4 vs 8.2; HR = 0.89 (95%CI: 0.69-1.15); P = 0.33
Sunitinib vs sorafenib (SUN, NCT00247676)	VEGFR, PDGFR, c-KIT, RET	1st	Sunitinib (n = 530) Sorafenib (n = 544)	< 7.2% vs < 6.9%, P = NR 50.8% vs 51.5%, P = 0.816	3.8 vs 4.1; HR = 1.13 (95%CI: 0.98-1.31); P = 0.16	7.9 vs 10.2; HR = 1.30 (95%CI: 1.13-1.5); P = 0.001
Ramucirumab vs placebo (REACH, NCT01140347)	VEGFR	2nd	Ramucirumab (n = 283) Placebo (n = 282)	7.1% vs < 0.7%, NR	3.5 vs 2.6; HR = 0.59 (95%CI: 0.49-0.72); P = 0.0001	9.2 vs 7.6; HR = 0.866 (95%CI: 0.72-1.05); P = 0.14
Everolimus vs placebo (EVOLVE-1, NCT01035229)	mTOR	2nd	Everolimus (n = 362) Placebo (n = 184)	2.2% vs 1.6%, P = NR 56.1% vs 45.1%, P = 0.01	3.0 vs 2.6; HR = 0.93 (95%CI: 0.75-1.15); P = NA	7.6 vs 7.3; HR = 1.05 (95%CI: 0.86-1.27); P = 0.67
Linifanib vs sorafenib (LIGHT, NCT01009593)	VEGFR, PDGFR	1st	Linifanib (n = 517) Sorafenib (n = 518)	13% vs 6.9%, P < 0.001 NR	5.4 vs 4.0; HR = 0.76 (95%CI: 0.64-0.89); P < 0.001	9.1 vs 9.8; HR = 1.04 (95%CI: 0.89-1.22); P = NS
Sorafenib + erlotinib vs sorafenib + placebo (SEARCH, NCT00901901)	EGFR	1st	Sorafenib + erlotinib (n = 362); Sorafenib + placebo (n = 358)	7% vs 4%, P = 0.051 44% vs 53%, P = 0.0104	3.2 vs 4.0; HR = 1.13 (95%CI: 0.94-1.36); P = 0.91	9.5 vs 8.5; HR = 0.92 (95%CI: 0.78-1.1); P = 0.2

CI: Confidence interval; EGFR: Epidermal growth factor receptor; DCR: Disease control rate; FGFR: Fibroblast growth factor receptor; HR: Hazard ratio; NA: Not applicable; NR: Not reported; NS: Not significant; OS: Overall survival; PDGFR: Platelet-derived growth factor receptor; PFS: Progression-free survival; RR: Response rate; TTP: Time to progression; VEGFR: Vascular endothelial growth factor receptor.