Table 2.
Selected studies on HAIC combinations as first-line treatment for advanced HCC.
| Group | Study Design | Patient Number (N) | Regimen | CP-B (%) | HBV (%) | PVT (%) | EHS (%) | ORR (%) | OS (Months) |
p-Value (OS) |
|---|---|---|---|---|---|---|---|---|---|---|
| INF-α | ||||||||||
| Sakon et al. [42] | Phase 2 single arm VP3–4, no EHS |
11 | 5-FU 450–500 mg/m2, Days 1–5 INF-α5MU qW1,3,5 |
54.5 | 36.4 | 100 | 0 | 72.7 | 8.0 | |
| Eun et al. [43] | Retrospective single arm |
31 | HAIC: 5-FU 750 mg/m2, cisplatin 25 mg/m2, Days 1–4 INF-α 3MU Days 1–4, then QOD |
19.4 | 83.9 | 100 | NR | 19.4 | 4.0 | 0.353 |
| 21 | HAIC alone: 5-FU 750 mg/m2, cisplatin 25 mg/m2, Days 1–4 |
19.0 | 85.7 | 100 | NR | 42.9 | 7.0 | |||
| Sorafenib | ||||||||||
| Ikeda et al. [44] | Randomized Phase 2 CPS-A, B7 |
65 | Cisplatin 65 mg/m2, Day 1 Every 4–6 weeks plus sorafenib |
12.3 | 33.8 | 61.5 | 29.2 | 21.7 | 10.8 | 0.031 |
| 41 | Sorafenib | 4.9 | 22.0 | 41.5 | 31.7 | 7.3 | 8.7 | |||
| Kudo et al. [45] | Phase 3 CPS-A, B7 |
102 | Cisplatin 20 mg/m2, Day 1, 8 5-FU 330 mg/m2 Days 1–5, 8–12 (every 4 weeks) Plus sorafenib |
11.7 | 25.5 | 56.9 | 26.5 | 36.0 (mRECIST) |
11.8 | 0.995 |
| 103 | Sorafenib | 9.7 | 21.4 | 62.1 | 25.2 | 18.0 (mRECIST) |
11.5 | |||
| Zhao et al. [46] | Retrospective CPS-A |
46 | Oxaliplatin 85 mg/m2, Day 1 (every 3 weeks) Plus sorafenib |
0 | 84.8 | 89.1 (VP3–4) |
19.6 | 34.8 | 9.4 | <0.01 |
| 58 | Sorafenib | 0 | 89.7 | 84.5 | 27.6 | 1.7 | 4.8 | |||
| He et al. [47] | Phase 3 PVT CPS-A |
125 | mFOLFOX 6, Days 1–3 (every 3 weeks) Plus sorafenib |
0 | 80.0 | 100 | 30.4 | 40.8 | 13.4 | <0.01 |
| 122 | Sorafenib | 0 | 81.1 | 100 | 34.4 | 2.5 | 7.1 | |||
| Lenvatinib | ||||||||||
| Mai et al. [48] | Retrospective Single arm |
24 | mFOLFOX 6, Days 1–3 (every 3 weeks) plus lenvatinib |
16.7 | 10.3 | NR | NR | 58.3 | 12 m OS 75% | |
| IO-based | ||||||||||
| Gu et al. [49] | Retrospective Single arm |
6 | mFOLFOX 6, Days 1–3 (every 3 weeks) Apatinib 250 mg QD (since D8) Toripalimab 240 mg D4, |
0 | NR | 100 | 33.3 | 100 | NR | |
| He et al. [50] | Retrospective | 71 | mFOLFOX 6, Days 1–3 Lenvatinib Toripalimab 240 mg per session |
0 | 87.3 | 77.5 | 22.5 | 59.2 | NR | <0.001 |
| 86 | Lenvatinib | 0 | 90.7 | 72.1 | 29.1 | 9.3 | 11 | |||
| RT | ||||||||||
| Han et al. [51] | Prospective Single arm PVT |
40 | 5-FU 500 mg/m2, Days 1–3 cisplatin 60 mg/m2, Day 2 plus RT |
0 | 92.5 | 100 | NR | 45 | 13.1 | |
| Katamura et al. [52] | Retrospective PVT |
16 | 5-FU 500 mg/m2, Days 1–5 plus RT |
25.0 | 25.0 | 100 | 37.5 | 75.0 | 7.5 | 0.871 |
| 16 | 5-FU 500 mg/m2, Days 1–5 | 18.8 | 31.3 | 100 | 25.0 | 25.0 | 7.9 | |||
| Fujino et al. [53] | Retrospective PVT, VP3–4 No EHS |
41 | cisplatin 20 mg/m2, Day 1, 8 5-FU 330 mg/m2 Days 1–5, 8–12 INF-α: recombinant 3MU or natural 5MU plus RT |
19.5 | 26.5 | 100 | 0 | 56.1 | 12.1 | 0.309 |
| 42 | HAIC plus INF-α as above | 23.8 | 23.8 | 100 | 0 | 33.3 | 7.2 | |||
| Kodama et al. [54] | Retrospective PVT and CPS-A, B7 |
68 | Cisplatin 20 mg/m2, day 1, 8 5-FU 330 mg/m2, Days 1–5, 8–12 (5-FU only in cycle 1–2) plus RT |
20.6 | 29.4 | 100 | 19.1 | 27.8 | 9.9 | 0.02 |
| 40 | Sorafenib | 12.5 | 42.5 | 100 | 40.0 | 6.7 | 5.3 |
aHCC: advanced hepatocellular carcinoma; CPS: Child–Pugh score; EHS: extrahepatic spread; HAIC: hepatic arterial infusion chemotherapy; HBV: hepatitis B virus; INF-α: interferon-alpha; MVI: macrovascular invasion; mRECIST: modified response evaluation criteria in solid tumors; NR: not reported; ORR: overall response rate; OS: overall survival; PVT: portal vein thrombosis; qW1,3,5: on Monday, Wednesday, Friday every week; QD: every day; QOD: every other day; TACE: transcatheter arterial chemoembolization; VP3: right/left portal vein; VP4: main portal vein; 5-FU: 5-fluorouracil.