Table 2.

Second line tyrosine kinase inhibitors approved for the treatment of advanced hepatocellular carcinoma

Study drug	Population	Design-intervention	Results
Regorafenib, Bruix et al[34], 2017, resorce	n = 553, BCLC B-C, ECOG 0-1, Child Pugh A, SOR-Tolerant	RCT phase III. Superiority. Regorafenib vs placebo	OS HR 0.63 (CI: 0.50-0.79), ORR 11%, DCR 65% (mRECIST)
Cabozantinib, Abou-Alfa et al[47], Celestial	n = 707, BCLC B-C, ECOG 0-1, Child Pugh A, 1-2 prior systemic treatment, SOR-Tolerant/intolerant	RCT phase III. Superiority. Cabozantinib vs placebo	OS HR 0.76 (CI: 0.63-0.93), ORR 4%, DCR 64% (RECIST 1.1)
Ramucirumab, Zhu et al[48], reach I-II	n = 542, BCLC B-C, ECOG 0-1, Child Pugh A, AFP ≥ 400 ng/mL, SOR-Tolerant/intolerant	RCT phase III. Superiority. Ramucirumab vs placebo	OS HR 0.69 (CI: 0.57-0.84), ORR 5%, DCR 60%, (RECIST 1.1)

Comparison across studies should cautiously analyzed. BCLC: Barcelona Clinic Liver Cancer; ECOG: Eastern Cooperative Oncology Group; OS: Overall survival; HR: Hazard ratio; SOR: Sorafenib; ORR: Objective response rate; RCT: Randomized clinical trials; DCR: Disease control rate; AFP: Alpha-fetoprotein.