Sequencing of systemic treatment for hepatocellular carcinoma: Second line competitors

Table 1 First line agents failed for the treatment of advanced hepatocellular carcinoma

Study drug	Population	Design-intervention	Results
Sunitinib (EGFR), Cheng et al[24], 2013	n = 1074, BCLC B-C, ECOG 0-1, Child Pugh A/B	RCT Fase III. Non-inferiority. Sunitinib vs Sorafenib	Failed to reach its primary end-point. Higher rate of EAs
Brivanib (VEGF, FGF), Johnson et al[25], 2013	n = 1150, BCLC B-C, ECOG 0-1, Child Pugh A/B	RCT Fase III. Non-inferiority. Brivanib vs Sorafenib (Bristol)	Failed to reach its primary end-point. Higher rate of EAs
Erlotinib (EGFR), Zhu et al[14], 2006	n = 720, BCLC B-C, ECOG 0-1, Child Pugh A/B	RCT Fase III. Superiority, Erlotinib + Sorafenib vs Placebo + Sorafenib	OS similar, TTP similar, Similar EAs
Linifanib (VEGF, PDGF), Cainap et al[27], 2015	n = 1035, BCLC B-C, ECOG 0-1, Child Pugh A/B	RCT Fase III. Superiority, Linifanib vs Sorafenib	Failed to reach its primary end-point. TTP better for linifanib, Similar EAs
Tigatuzumab, Bruix et al[30], 2017	n = 162, BCLC B-C, ECOG 0-1, Child Pugh A/B	RCT Fase II, Tigatuzumab + Sorafenib vs Placebo + Soraf	Safety profile adequate but no better TTP and OS
Dovitinib (VEGF, FGF, PDGF), Cheng et al[28], 2016	n = 165, BCLC B-C, ECOG 0-1, Child Pugh A/B	RCT Fase II. Dovitinib vs Sorafenib	OS non superior, TTP similar, Higher rate of EAs
Bevacizumab (Ab VEGF), Hubbard et al[29], 2016	n = 17, BCLC B-C, ECOG 0-1, Child Pugh A/B	RCT Fase I/II, Bevacizumab + Sorafenib	Higher rate of EAs, Excessive toxicity

BCLC: Barcelona Clinic Liver Cancer; ECOG: Eastern Cooperative Oncology Group; EGFR: Endothelial growth factor; FGF: Fibroblast growth factor; OS: Overall survival; PDGF: Platelet-derived growth factor inhibitor; TTP: Time to progression; VEGF: Vascular-endothelial growth factor; RCT: Randomized clinical trials.