Table 1.
Characteristics of the included trials.
| Author | Year | Trial | RCT phase | Treatment Arm | Comparative Arm | Patients number | Region | Male | Mean/median age | HBV | HCV | Child A | BCLC C | PVI | EHS | Outcome |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Llove (11) | 2008 | SHARP | III | Sorafenib | Placebo | 602 | US Eu AusNZ | 87.0% | 65.6 | 18.4% | 28.1% | 96.5% | 82.4% | 38.4% | 51.3% | OS, PFS, AEs |
| Cheng (19) | 2009 | NCT00492752 | III | Sorafenib | Placebo | 226 | AP | 85.4% | 52.5 | 73% | 8.4% | 97.3% | 95.6% | 35.4% | 68.6% | OS, PFS, AEs |
| Cheng (20) | 2013 | SUN1170 | III | Sunitinib | Sorafenib | 1074 | AP | 83.3% | 55.1 | 53.8% | 21.6% | 99.6% | 85.3% | 32.1% | – | OS, PFS |
| Johnson (21) | 2013 | BRISK-FL | III | Brivanib | Sorafenib | 1155 | US Eu AP AusNZ | 83.7% | 57.8 | 44.3 | 20.3% | 92.0% | 77.3% | 19.3% | 49.7 | OS, PFS, AEs |
| Cheng (22) | 2015 | NCT01033240 | II | Tigatuzumab plus Sorafenib | Sorafenib | 162 | AP US | 82.7% | 63 | 50% | 33.9% | 100.0% | – | – | – | OS, PFS, AEs |
| Cainap (23) | 2015 | NCT01009593 | III | Linifanib | Sorafenib | 1035 | US Eu AP AusNZ | 85% | 56.6 | 53.2% | 25% | 94.4% | 82.2% | 43.4% | 58.3% | OS, PFS, AEs |
| Zhu (24) | 2015 | SEARCH | III | Erlotinib plus Sorafenib | Sorafenib | 720 | US Eu AP | 80.7% | – | 35.4% | 26.5% | 97.4% | 85% | 40.4% | 58.9% | OS, PFS, AEs |
| Kudo (25) | 2017 | NCT02400788 | II | Resminostat plus Sorafenib | Sorafenib | 164 | AP | – | – | – | – | – | – | – | – | OS |
| Kudo (12) | 2018 | REFLECT | III | Lenvatinib | Sorafenib | 954 | US Eu AP | 84.0% | 58.0 | 50% | 23.0% | 99.0% | 79.0% | 21.0% | 61.0% | OS, PFS, AEs |
| Abou-Alfa (26) | 2019 | CALGB80802 | III | Sorafenib plus doxorubicin | Sorafenib | 356 | AP US Canada | 67.1% | 62 | 9.3% | 19.7% | 100.0% | – | – | – | OS, PFS |
| Yau (27) | 2019 | CheckMate 459/III | III | Nivolumab | Sorafenib | 743 | AP, Eu, US, Canada | 85% | 65 | – | – | – | – | – | – | OS |
| Assenat (28) | 2019 | NCT00941967 | II | Sorafenib | Sorafenib plus GEMOX | 83 | Eu | 89.2% | 62 | 3.6% | 15.7% | – | 85.5% | 26.5% | 68.7% | PFS, AEs |
| Qin (29) | 2020 | NCT02645981 | II–III | Donafenib | Sorafenib | 659 | AP | 86.8% | 53 | 90.1% | 1.8% | 97.4% | 87.4% | 73.4% | 31.4% | OS, PFS, AEs |
| Finn (13) | 2020 | IMbrave150 | III | Atezolizumab plus Bevacizumab | Sorafenib | 501 | AP, US, Australia, Eu | 82.6% | 64 | 47.9% | 8.6% | 100.0% | 81.6% | 39.9% | 60.9% | OS, PFS, AEs |
| Ren (14) | 2021 | NCT03794440 | II–III | Sintilimab plus bevacizumab | Sorafenib | 571 | AP | 88.4% | 53 | 94.2% | 2.5% | 95.8% | 85.5% | 27.1% | 74.1% | OS, PFS, AEs |
US, the United State; Eu, Europe; AP, Asia-Pacific; HBV, hepatitis Bvirus; HCV, hepatitis C virus; BCLC, Barcelona Clinic Liver Cancer; PVI, portal vein invasion; EHS, extrahepatic spread; OS, overall survival; PFS, progression-free survival; AEs, adverse events.
Brivanib, a small-molecule tyrosine kinase inhibitor, is the first oral selective dual inhibitor of fibroblast growth factors (FGF) and vascular endothelial growth factor (VEGF) signaling.