Table 1.
Clinical trials of systemic therapy in HCC
| Therapy | Time | Trial | Line | Drug | Control | Primary outcomes (HR; 95% CI) |
|---|---|---|---|---|---|---|
| Targeted therapy | ||||||
| 2005 | NCT00033462 | First | Erlotinib | None | 6-month PFS rate: 32% | |
| 2007 | SHARP | First | Sorafenib | Placebo | OS: 10.7 vs. 7.9 (0.69; 0.55–0.87) | |
| 2008 | Asia-Pacific | First | Sorafenib | Placebo | OS: 6.5 vs. 4.2 (0.68; 0.50–0.93) | |
| 2011 | NCT00699374 | First | Sunitinib | Sorafenib | OS: 7.9 vs. 10.2 (1.3; 1.13–1.5) | |
| 2011 | NCT00604721 | First | Selumetinib | None | TTP: 2 | |
| 2012 | BRISK-FL | First | Brivanib | Sorafenib | OS: 9.5 vs. 9.9 (1.06; 0.93–1.22) | |
| 2012 | BRISK-PS | Second | Brivanib | Placebo | OS: 9.4 vs. 8.2 (0.89; 0.69–1.15) | |
| 2013 | NCT00427973 | First | Cediranib | None | 3-month PFS rate: 77% | |
| 2014 | EVOLVE-1 | Second | Everolimus | Placebo | OS: 7.6 vs. 7.3 (1.05; 0.86–1.27) | |
| 2015 | NCT01210495 | Second | Axitinib | None | 16-week DCR rate: 42.3% | |
| 2015 | REACH | Second | Ramucirumab | Placebo | OS: 9.2 vs. 7.6 (0.87; 0.72–1.05) | |
| 2016 | NCT01232296 | First | Dovitinib | Sorafenib | OS: 8.0 vs. 8.4 (1.27; 0.90–1.79) | |
| 2017 | RESORCE | Second | Regorafenib | Placebo | OS: 10.6 vs. 7.8 (0.63; 0.50–0.79) | |
| 2018 | REFLECT | First | Lenvatinib | Sorafenib | OS: 13.6 vs. 12.3 (0.95; 0.79–1.06) | |
| 2018 | NCT01004003 | First | Nintedanib | Sorafenib | TTP: 5.5 vs. 4.6 (1.44; 0.81–2.57) | |
| 2018 | NCT01915589 | First | Refametinib | None | ORR: 0%; DCR: 56.3% | |
| 2018 | METIV-HCC | Second | Tivantinib | Placebo | OS: 8.4 vs. 9.1 (0.97; 0.75–1.25) | |
| 2019 | CELESTIAL | Second | Cabozantinib | Placebo | OS: 10.2 vs. 8.0 (0.76; 0.63–0.92) | |
| 2019 | REACH-2 | Second | Ramucirumab | Placebo | OS: 8.5 vs. 7.3 (0.71; 0.531–0.949) | |
| 2020 | NCT02645981 | First | Donafenib | Sorafenib | OS: 12.1 vs. 10.3 (0.831; 0.699–0.988) | |
| 2020 | NCT02329860 | Second | Apatinib | Placebo | OS: 8.7 vs. 6.8 (0.785; NA) | |
| Immunotherapy | ||||||
| 2013 | NCT01008358 | First | Tremelimumab | None | PR: 17.6%; DCR: 76.4% | |
| 2017 | Checkmate-040 | Second | Nivolumab | None | ORR: ~ 17% | |
| 2018 | KEYNOTE-224 | Second | Pembrolizumab | None | ORR: 17% | |
| 2019 | Checkmate-459 | First | Nivolumab | Sorafenib | OS: 16.4 vs. 14.7 (0.85; 0.72–1.02) | |
| 2019 | KEYNOTE-240 | Second | Pembrolizumab | Placebo | PFS: 3.0 vs. 2.8 (0.718; 0.570–0.904) | |
| 2020 | NCT02989922 | Second | Camrelizumab | None | ORR: 14.7% | |
OS, overall survival; PFS, progression-free survival; DCR: disease control rate; TTP: time to progression; PR: partial response; ORR: object response rate; HR, hazard ratio; CI, confidence interval
* Primary outcomes (months or rate)