Table 1.
Key phase III clinical trials of US FDA approved therapies in hepatocellular carcinoma.
| Study (n) | Regimen or Drug(s) Evaluated | Molecular Targets | ORR (%) | mPFS (Months) |
mOS (Months) |
|---|---|---|---|---|---|
| SHARP (n = 602) | Sorafenib 400 mg twice daily compared to placebo | VEGFRs 1–3, PDGFR, RAF, and c-kit | 2 | 4.1 | 10.7 |
| Asia-Pacific (n = 226) | 3.3 | 2.8 | 6.5 | ||
| CALGB 80802 (n = 356) | Sorafenib 400 mg twice a day (S) compared to sorafenib + doxorubicin (D) | S + D: 9.3 S: 5.4 |
4 (S + D) 3.9 (S) |
9.3 (S + D) 9.4 (S) |
|
| REFLECT (n = 954) | Lenvatinib 12 mg/day (>60 kg body weight), Lenvatinib 8 mg/day (<60 kg body weight) compared to sorafenib 400 mg twice daily |
FGFR 1–4, EGFR 1–3, PDGFR, and c-kit |
lenvatinib: 24.1, Sorafenib: 9.2 |
Lenvatinib: 7.4 Sorafenib: 3.7 |
Lenvatinib: 13.6 Sorafenib: 12.3 |
| IMbrave 150 (n = 501) | Atezolizumab 1200 mg + bevacizumab 15 mg/kg (A + B) compared to sorafenib (S) | PD-L1, VEGF | A + B: 30 S: 11.3 |
A + B: 6.9 S: 4.3 |
A + B: 19.2 S: 13.4 |
| CheckMate 459 (n = 743) | Nivolumab 240 mg/ 2 weeks (N) * compared to sorafenib 400 mg twice daily (S) | PD-1 | N: 15 S: 7 |
Nivolumab: 3.7 Sorafenib: 3.8 |
Nivolumab: 16.4 Sorafenib: 14.7 |
| CheckMate 040 | Ipilimumab and Nivolumab ^* | PD-1, CTLA4 | 32% (Arm A) 27% (Arm B) 29% (Arm C) |
- | Arm A: 22.8 Arm B: 12.5 Arm C:12.8 |
| KEYNOTE-224 (n = 104) |
Pembrolizumab * | PD-1 | 18.3 | 4.9 | 13.2 |
| CELESTIAL (n = 707) | Cabozantinib 60 mg/day compared to placebo | AXL, MET, and VEGFR2 | 4 | 5.2 | 10.2 |
| RESORCE (n = 573) | Regorafenib 160 mg/day compared to placebo | VEGFR 1–3, FGFR, PDGFR, and c-kit | 11 | 3 | 10.6 |
| REACH (n = 565) | Ramucirumab 8 mg/kg compared to placebo | VEGFR-2 | 7 | 2.8 | 9.2 |
| REACH-2 (n = 292) | 5 | 2.8 | 8.5 |
ORR: Overall Response Rate Per HCC specific modified RECIST criteria; mPFS: median Progression Free Survival of the cohort receiving active agent; mOS: median Overall Survival of the cohort receiving active agent; VEGFR: Vascular endothelial growth factor receptor; RAF: Rapidly accelerated fibrosarcoma; EGFR: Epidermal growth factor receptor; FGFR: Fibroblast growth factor receptor; PDGFR: Platelet-derived growth factor receptor; PD-1/PD-L1: programmed death-ligand 1. ^ Arm A: nivolumab 1 mg/kg plus ipilimumab 3 mg/kg, administered every 3 weeks (4 doses), followed by nivolumab 240 mg every 2 weeks; Arm B: nivolumab 3 mg/kg plus ipilimumab 1 mg/kg, administered every 3 weeks (4 doses), followed by nivolumab 240 mg every 2 weeks; Arm C: nivolumab 3 mg/kg every 2 weeks plus ipilimumab 1 mg/kg every 6 weeks. * Not approved by European Medical Agency for the use in European Union.