Skip to main content

Advertisement

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
  1. PFS Progression-free survival, OS Overall survival, DCR Disease control rate. EGFR Epidermal growth factor receptor, Tie2 Angiopoietin receptor, FGFR Fibroblast growth factor receptor, PDGFR Platelet-derived growth factor receptor, VEGFR Vascular endothelial growth factor receptor, RET Glial cell-derived neurotrophic factor receptor, C-MET Hepatocyte growth factor receptor, KIT Stem cell factor receptor