Table 2. Main characteristics of drugs tested in second line trials post sorafenib.
| Regorafenib10 | Cabozantinib11 | Ramucirumab12 | Pembrolizumab14 | Nivolumab13 | Nivolumab25 | |
|---|---|---|---|---|---|---|
| Ph III | Ph III | Ph III | Ph II | Ph II | Doc FDA | |
| N | 379 | 470 | 197 | 104 | 57 | 154 |
| Intol/progr % | 0/100 | ?/? | 16/84 | 20/80 | 0/100 | ?/? |
| Sorafenib (duration) | 7.8 m | 5.3 m | UK | 6.8 | UK | UK |
| EHS (%) | 70 | 79 | 71.6 | 64 | UK | 71 |
| MVI (%) | 29 | 27 | 35.5 | 17 | UK | 29 |
| % AFP high (limit) | 43 (400) | 41 (400) | 100 (400) | 41 (200) | UK | 37 (400) |
| RR (RECIST 1.1) | 7% | 4% | 4.6% | 17% | 21% | 14.3% |
| DCR (%) | 66 | 64 | 59.9 | 62 | 61 | UK |
| PD (%) | 22 | 21 | 33.5 | 33 | 32 | – |
| TTP (months) | 3.2 | UK | – | 4.9 | – | – |
| PFS (months) | 3.1 | 5.2 | 2.8 | 4.9 | 4.0 | – |
| mOS (months) | 10.6 | 10.2 | 8.5 | 12.9 | 13.2 | – |
| mOS: HR | 0.63 | 0.76 | 0.71 | – | – | – |
| Tt (duration) | 3.6 | 3.8 | UK | 4.2 | UK | UK |
| Response (duration) | 3.5 | UK | UK | 9+ | ? | 12+ ? |
| Cessation/tox (%) | 25 | 16 | 10.7 | 5 | 4 | – |
| Dose intensity (%) | 90 | 60 | 98 | UK | UK | UK |
DCR: Disease control rate; EHS: Extrahepatic spread; HR: Hazard ratio; Intol: Intolerant to sorafenib; m: Months; mOS: Median overall survival; MVI: Macroscopic venous invasion; PD: Progressive disease; PFS: Progression-free survival; Progr: Progressor on sorafenib; RECIST 1.1: Response evaluation criteria in solid tumors version 1.1; RR: Response rate; tox: Toxicity; Tt: Treatment; TTP: Time to progression; UK: Unknown.