Table 1.
The History of Agents Used in the Treatment of HCC
| Name of the Agent | Trial | Date | Hazard Ratio (95% CI) and OS (Months) |
|---|---|---|---|
| 1st Line | |||
| Doxorubicin vs No therapy | Doxorubicin vs no antitumor therapy in aHCC. A prospective randomized trial | 1988 | 10.6 weeks vs 7.5 weeks (p = 0.036)44 |
| Sorafenib vs Placebo | SHARP trial (phase III) | 2008 | 0.69 (0.55–0.87); 10.7 vs 7.928 |
| Sorafenib vs Placebo | Asia-Pacific trial (phase III) | 2009 | 0.68 (0.50–0.93); 6.5 vs 4.230 |
| Sunitinib vs Sorafenib | SUN1170 (phaseIII) | 2013 | 1.30 (1.13−1.50); 7.9 vs 10.251 |
| Brivanib vs Sorafenib | BRISK-FL (phase III) | 2013 | 1.06 (0.93−1.22); 9.5 vs 9.952 |
| Linifanib vs Sorafenib | LIGHT (phase III) | 2014 | 1.046 (0.896−1.221); 9.1 vs 9.853 |
| Sorafenib + Erlotinib vs Sorafenib alone | SEARCH (phase III) | 2015 | 0.929 (0.781–1.106); 9.5 vs 8.556 |
| Y40 vs Sorafenib | SARAH (phase III) | 2017 | 1.15 (0.94–1.41); 8.0 vs 9.954 |
| Y40 vs Sorafenib | SIRveNIB (phase III) | 2018 | 1.1(0.9−1.4); 8.8 vs 10.055 |
| Lenvatinib vs Sorafenib (non- inferiority) | REFLECT (phase III) | 2018 | 0.92 (0.79–1.06); 13.6 vs 12.350 |
| Sorafenib + Doxorubicin vs Sorafenib alone | ALLIANCE (CALGB 80802) (phase III) | 2019 | 1.05 (0.83–1.31); 9.3 vs 9.423 |
| Nivolumab vs Sorafenib | CheckMate 459 (phase III) | 2019 | 0.85 (0.72–1.02); 16.4 vs 14.770 |
| Atezolizumab plus Bevacizumab vs Sorafenib | IMbrave150 (phase III) | 2020 | 0.58 (0.42–0.79); 6-mo OS: 84.8% vs 67.2% 12-mo OS: 72.2% vs 54.6%18 |
| 2nd Line | |||
| Regorafenib | RESORCE (phase III) | 2016 | 0.63 (0.50–0.79); 10.6 vs 7.816 |
| Nivolumab | CheckMate 040 (phase I/II) | 2017 | OS (95% CI): 15.1 (13.2–18.2)67 |
| Cabozantinib | CELESTIAL (phase III) | 2018 | 0.76 (0.63–0.92); 10.2 vs 8.060 |
| Ramucirumab | REACH (phase III) | 2015 | 0.87 (0.72–1.05) 9.2 vs 7.663 |
| Ramucirumab | REACH-2 (phase III) | 2018 | 0.71 (0.53–0.95) 8.5 vs 7.364 |
| Pembrolizumab | KEYNOTE-224 (phase II) | 2018 | OS (95% CI): 13.2 (9.7–15.5), 1-year OS (95% CI): 54% (44–63)68 |
| Pembrolizumab | KEYNOTE-240 (phase III) | 2020 | 0.78 (0.61–1.00) 13.9 vs 10.669 |
| Nivolumab plus Ipilimumab | CheckMate 040 (phase II) | 2020 | 22.8 (9.4-not reached), 1-year OS (95% CI): 61% (46–73%), 2-year OS (95% CI): 48% (34–61%)80 |
Abbreviations: aHCC, advanced hepatocellular carcinoma; vs, versus; Y-40, Yttrium-40; OS, overall survival.