Table 1 Clinical research on molecular targeted drugs for hepatocellular carcinoma
From: Molecular targeted and immune checkpoint therapy for advanced hepatocellular carcinoma
Drug | Study phase | Trial name | Publication time | Combination | Versus | Fist author | Result | Primary end point | Targets/Pathway |
|---|---|---|---|---|---|---|---|---|---|
First-line systemic therapy | |||||||||
Sorafenib | III | SHARP | 2008 | / | placebo | M. Llovet | Positive | OS: 10.7 months | VEGFR1/2/3; PDGFR;Ras/Raf/Mek/Erk |
III | ORIENTAL | 2009 | / | placebo | Ann-Lii Cheng | Positive | OS: 6.5 months | ||
Lenvatinib | II | / | 2017 | / | single-arm | Kenji Ikeda | Positive | OS: 18.7 months | VEGFR1/2/3; FGFR1/2/3/4; FGF; PDGFR2; RET |
III | REFLECT | 2018 | / | sorafenib | Masatoshi | Positive | OS: 13.6 months PFS: 8.9 months | ||
Second-line systemic therapy | |||||||||
Multitarget tyrosine inhibitor | |||||||||
Regorafenib | II | / | 2013 | / | single-arm | Jordi Bruix | Positive | OS: 13.8 months | VEGFR1; RETRAF1; TIE-2; BRAF; PDGFR; FGFR; |
III | RESORCE | 2017 | / | placebo | Jordi Bruix | Positive | OS: 10.6 months | ||
Cabozantinib | II | / | 2017 | / | placebo | R.K. Kelley | Positive | OS: 11.5 months | c-Met; VEGFR1/2/3 |
III | CELESTIAL | 2018 | / | placebo | Abou-Alfa | Positive | OS: 10.2 months PFS: 5.2 months | ||
VEGF receptor inhibitor | |||||||||
Ramucirumab | III | REACH | 2015 | / | placebo | Andrew X Zhu | Negative | OS: 9.2 months | VEGFR2 |
III | REACH-2 | 2019 | / | placebo | Andrew X Zhu | Positive | OS: 8.5 months | ||
Anti-PD-1 antibody | |||||||||
Nivolumab | I/II | CheckMate −040 | 2017 | / | single-arm | El-Khoueiry | Positive | OS: 15 months | PD-1 |
Pembrolizumab | II | KEYNOTE − 242 | 2018 | / | single-arm | Andrew X Zhu | Positive | OS: 12.9 months | PD-1 |
Other targeted therapies | |||||||||
Antiangiogenic drugs | |||||||||
Bevacizumab | II | / | 2006 | GEMOX | single-arm | Andrew X Zhu | Positive | OS: 9.6 months | VEGF |
Brivanib | II | / | 2011 | / | single-arm | JW Park | Positive | OS: 10 months PFS: 2.7 months | VEGF; FGFR |
III | BRISK-PS | 2013 | / | placebo | M. Llovet | Negative | OS: 9.4 months | ||
III | BRISK-FL | 2013 | / | sorafenib | PJ. Johnson | Negative | OS: 9.5 months | ||
Linifanib | II | / | 2013 | / | single-arm | Han Chong | Positive | OS: 9.7 months PFS: 3.7 months | VEGF; PDGFR |
III | LiGHT | 2015 | / | sorafenib | Calin Cainap | Negative | OS: 9.1 months TTP: 5.4 months | ||
Sunitinib | II | / | 2009 | / | single-arm | Andrew X Zhu | Positive | OS: 9.8 months PFS: 3.9 months | VEGFR; PDGFRa/b; c-Kit; |
III | SUN1170 | 2013 | / | sorafenib | Ann-Lii Cheng | Negative | OS: 7.9 months PFS: 3.6 months | ||
Immunoreactive drugs | |||||||||
Tremelimumab | I | / | 2017 | ablation | single-arm | Duffy AG | Positive | OS: 12.3 months TTP: 7.4 months | CTLA-4 |
II | / | 2013 | / | single-arm | Sangro B | Positive | OS: 8.2 months TTP: 6.5 months | ||
Drugs targeting EGFR | |||||||||
Erlotinib | II | / | 2018 | bevacizumab | sorafenib | Thomas | Negative | OS: 8.55 months PFS: 4.37 months | EGFR |
III | SEARCH | 2015 | sorafenib | placebo | Andrew X Zhu | Negative | OS: 9.5 months | ||
Cetuximab | II | / | 2008 | GEMOX | single-arm | Asnacios | Positive | OS: 9.5 months PFS: 4.7 months | EGFR |
II | / | 2010 | / | single-arm | Andrew X Zhu | Negative | OS: 9.6 months PFS: 1.4 months | ||
II | / | 2011 | XELOX | single-arm | Sanoff | Negative | TTP: 4.5 months DCR: 83% | ||
Lapatinib | II | / | 2009 | / | single-arm | TB-Saab | Negative | OS: 12.6 months PFS: 1.9 months | EGFR |
Drugs targeting PI3K/Akt/mTOR signal pathway | |||||||||
Sirolimus | I | / | 2008 | / | single-arm | Magnus Rizell | Positive | OS: 6.5 months | PI3K/Akt/mTOR |
II | / | 2012 | / | single-arm | Thomas | Positive | OS: 6.6 months PFS: 3.8 months | ||
Everolimus | I/II | / | 2011 | / | single-arm | Andrew X Zhu | Negative | OS: 8.4 months | PI3K/Akt/mTOR |
III | EVOLVE-1 | 2014 | / | placebo | Andrew X Zhu | Negative | OS: 7.6 months PFS: 3.0 months | ||
C-Met inhibitor | |||||||||
Tivantinib | II | / | 2013 | / | placebo | Santoro | Positive | PFS: 2.7 months | C-Met |
III | METIV-HCC | 2018 | / | placebo | Rimassa | Negative | OS: 8.4 months | ||