Table 1.
FDA-approved first- and second-line systemic therapies for advanced HCC.
| Drug | Targets | First/ Second Line |
OS (Months) | PFS (Months) | n | Year | Phase III Trial |
|---|---|---|---|---|---|---|---|
| Sorafenib | VEGFRs 1-3, PDGFR-β, Raf-1, B-Raf | First | 10.7 vs. 4.9 (placebo) 6.5 vs. 4.2 (placebo) |
5.5 vs. 2.8 2.8 vs. 1.4 |
602 226 |
2008 2009 |
SHARP ORIENTAL |
| Lenvatinib | VEGFRs 1–3, FGFRs 1–4, PDGFR-α, RET, KIT | First | 13.6 vs. 12.3 (sorafenib) | 7.4 vs. 3.7 | 954 | 2018 | REFLECT |
| Atezolizumab and Bevacizumab | PD-L1 and VEGF | First | 19.2 vs. 13.4 (sorafenib) | 6.8 vs. 4.3 | 501 | 2020 | IMBrave 150 |
| Tremelimumab and Durvalumab | CTLA-4 and PD-L1 | First | 16.4 vs. 13.8 (sorafenib) | 3.8 vs. 4.1 | 782 | 2022 | HIMALAYA |
| Regorafenib | VEGFR, FGFR, PDGFR, B-RAF, RET and KIT | Second | 10.6 months vs. 7.8 (placebo) | 3.1 vs. 1.5 | 573 | 2017 | RESOURCE |
| Pembrolizumab | PD-1 | Second | 13.9 vs. 10.6 (placebo) | 3.0 vs. 2.8 | 413 | 2018 | KEYNOTE 240 |
| Cabozantinib | VEGFR, AXL, c-MET, KIT, RET | Second | 10.2 vs. 8.0 (placebo) | 5.2 vs. 1.9 | 707 | 2019 | CELESTIAL |
| Ramucirumab | VEGFR 2 | Second | 8.5 vs. 7.3 (placebo) | 2.8 vs. 1.6 | 292 | 2019 | REACH-2 |
| Nivolumab and Ipilimumab | PD-1 and CTLA-4 | Second | Arm A: 22.8 Arm B: 12.5 Arm C: 12.7 |
Arm A: 17.0 Arm B: 22.2 Arm C: 16.6 |
148 | 2020 | CHECK-MATE 040 |
Arm A: 1 mg/kg of nivolumab and 3 mg/kg of ipilimumab every 3 weeks (4 doses), then 240 mg of nivolumab every 2 weeks. Arm B: 3 mg/kg of nivolumab and 1 mg/kg of ipilimumab every 3 weeks (4 doses), then 240 mg of nivolumab every 2 weeks. Arm C: 3 mg/kg of nivolumab every 2 weeks and 1 mg/kg of ipilimumab every 6 weeks.