Table 2:
Systemic therapies approved for HCC: patients characteristics and outcomes.
| Study name | Treatment | Inhibited molecules | BCLC (0/A/B/C) % |
Previous local therapies % |
MVI % |
EHD % |
ECOG PS (0/1/2) % |
Child-Pugh A % |
Median OS (HR, 95% CI) | Median PFS (HR, 95% CI) | ORR mRECIST; RECIST % |
|---|---|---|---|---|---|---|---|---|---|---|---|
| First-line therapies | |||||||||||
| IMbrave15018,141 | Atezolizumab + bevacizumab | PDL1 (immune checkpoint) VEGF (angiogenesis) | - / 2 / 15 / 82 | 48 | 38 | 63 | 62 / 38 / - | 100 | 19.2mo (0.66, 0.52–0.85) |
6.9mo (0.65, 0.53–0.81) | 35.4; 29.8 |
| SHARP13 (IMbrave150, REFLECT) | Sorafenib | VEGFR, PDGFR (angiogenesis) MAPK (BRAF) |
- / - / 18 / 82 | 67 | 36 | 53 | 54 / 38 / 8 | 95 | 10.7–13.4moa (0.69, 0.55–0.87)b | 3.7–4.3moa (NR)b |
NR; 2 |
| REFLECT14 | Lenvatinib | VEGFR, PDGFR, FGFR (angiogenesis) KIT, RET |
- / - / 22 / 78 | 78 | 23 | 61 | 64 / 36 / - | 99 | 13.6mo (0.92, 0.79–1.06) | 7.4mo (0.66, 0.57–0.77) |
24.1; 18.8 |
| Second-line therapies | |||||||||||
| RESORCE15 | Regorafenib | VEGFR, PDGFR (angiogenesis) MAPK (BRAF) |
- / <1 / 14 / 86 | 85 | 29 | 70 | 65 / 35 / - | 98 | 10.6mo (0.63, 0.5–0.79) | 3.1mo (0.46, 0.37–0.56) | 11; 7 |
| CELESTIAL16 | Cabozantinib | MET (proliferation) VEGFR (angiogenesis) RET |
- / - / 9 / 91 | 44c | 27 | 79 | 52 / 48 / <1 | 98 | 10.2mo (0.76, 0.63–0.92) | 5.2mo (0.44, 0.36–0.52) | NR; 4 |
| REACH-217 | Ramucirumab (AFP>400 ng/dL) | VEGFR2 (angiogenesis) | - / - / 17 / 83 | 62d | 36 | 72 | 57 / 43 / - | 100 | 8.5mo (0.71, 0.53–0.95) | 2.8mo (0.45, 0.34–0.6) | NR; 5 |
| KEYNOTE-240136 | Pembrolizumab | PD1 (immune checkpoint) | - / - / 20 / 80 | NR | 13 | 70 | 58 / 42 / - | 100 | 13.9mo (0.78, 0.61–1) | 3mo (0.78, 0.61–0.99) | NR; 18 |
| KEYNOTE-22419 | Pembrolizumab | PD1 (immune checkpoint) | - / - / 24 / 76 | NR | 17 | 64 | 61 / 39 / - | 94 | 13.2mo | 4.9mo | 15; 18.3 |
| CheckMate 04021 | Nivolumab + ipilimumab (Arm A) |
PD1 and CTLA4 (immune checkpoints) | 2 / 4 / 8 / 86 | ≥72 | 36 | 80 | NR | 100 | 22.8mo | NR | NR; 32 |
This range corresponds to the reported survival data in SHARP (experimental arm), REFLECT and IMbrave150 (control arm).
The Hazard Ratio corresponds to the phase 3 SHARP trial that compared sorafenib with placebo.
Includes only liver-directed non-radiation therapies.
Includes only surgical procedures and radiotherapy. AFP, alpha-fetoprotein; BCLC, Barcelona Clinic Liver Cancer stage; CI, Confidence Interval; CTLA4, cytotoxic T-lymphocyte antigen 4; ECOG PS, Eastern Cooperative Oncology Group performance status; EHD, extrahepatic disease; FGFR, fibroblast growth factor receptor; HCC, hepatocellular carcinoma; MVI, macrovascular invasion; HR, Hazard Ratio; mRECIST, modified RECIST; NR, not reported; RECIST, Response Evaluation Criteria In Solid Tumors; OS, overall survival; ORR, overall response rate; PD1, programmed cell death protein 1; PD-L1, programmed death ligand 1; PDGFR, platelet-derived growth factor receptor; PFS, progression-free survival; VEGFR, vascular endothelial growth-factor receptor.