Table 1.
Tyrosine kinase inhibitors for the treatment of advanced HCC.
| TKI | Trial | Comparison | Setting | Clinical Features of Enrolled Patients (%) | OS | PFS/TTRP * | ORR/DCR ** | Grade 3–4 AEs |
|---|---|---|---|---|---|---|---|---|
| Sorafenib (Nexavar) |
SHARP (Phase III) [37] |
Placebo | First-line | - Child–Pugh Stage A (97%), Westerns - HCV (29%), alcohol intake, HBV (19%) - Extrahepatic disease (51%) - Macroscopic vascular invasion (70%) |
10.7 vs. 7.9 months; HR = 0.69; p < 0.001 |
5.5 vs. 2.8 months; HR = 0.58; p < 0.001 * |
43% vs. 32%; p = 0.002 ** |
8% vs. 2%; p < 0.001 |
| Sorafenib (Nexavar) |
ASIAN PACIFIC (Phase III) [38] |
Placebo | First-line | - Child–Pugh Stage A (97%), Orientals - HBV (71%), HCV (11%) - Extrahepatic disease (69%) - Macroscopic vascular invasion (35%) |
6.5 vs. 4.2 months; HR = 0.68; p = 0.014 |
2.8 vs. 1.4 months; HR = 0.57; p = 0.0005 |
35% vs. 16%; p = 0.0019 ** |
9% vs. 1% |
| Lenvatinib (Lenvima) |
REFLECT (Phase III) [39] |
Sorafenib | First-line | - Child–Pugh Stage A (99%) - Westerners (30%), Asians (70%) - HBV (53%), HCV (19%) - Extrahepatic disease (60%) - No ≥ 50% liver tumor burden, gross invasion of the bile duct or the main portal vein |
13.6 vs. 12.3 months; HR = 0.92 |
7.4 vs. 3.7 months; HR 0.66; p < 0.0001 |
24.1%vs. 9.2%; p < 0.0001 75% vs. 60% |
75% vs. 67% |
| Cabozantinib (Cometriq, Cabometyx) |
CELESTIAL (Phase III) [40] |
Placebo | Second-/Third-line | - Child–Pugh Stage A (98%), Westerns (70%) - HBV (38%), HCV (25%) - Extrahepatic disease (80%) - Macrovascular invasion (30%) |
10.2 vs. 8.0 months; HR = 0.76; p <0.001 |
5.2 vs. 1.9 months; HR = 0.44; p < 0.001 |
4% vs. 0.4%; p = 0.009/ 64% vs. 48%; p < 0.001 ** |
68% vs. 36% |
| Regorafenib (Stivarga) |
RESORCE (Phase III) [41] |
Placebo | Second-line | - Child–Pugh Stage A (98%), Orientals (40%) - HBV (38%), alcohol intake (25%), HCV (21%) - Extrahepatic disease (70%) - Macrovascular invasion (30%) |
10.6 vs. 7.8 months; HR = 0.63; p < 0.0001 | 3.1 vs. 1.5 months; HR = 0.46; p < 0.001; 3.2 vs. 1.5 months; HR = 0.44; p < 0.001 * |
10.6% vs. 4.1%; p = 0.005 65.2% vs. 36%; p = 0.001 |
44% vs. 47% |
Abbreviations: tyrosine kinase inhibitor (TKI); Progression free-Survival (PFS); Overall Survival (OS); Objective Response Rate (ORR); Time to Radiological Progression (TTRP) *; Disease Control Rate (DCR) **.