Table 2.
Characteristics of included study
| Author, year | Registered number, Acronym |
Phase | Region | Study design | Baseline characteristics of study population | |||
|---|---|---|---|---|---|---|---|---|
| Age (years) (mean or median) | Male (%) | BCLC stage (%) | Child–Pugh class (%) | |||||
| Kudo 2021 [32] |
CheckMate 040 |
1/2 | Multi-centre |
• Non-Randomized • Parallel Assignment • Open Label |
67 | NA |
4(A), 16(B), 73(C), NR(D) |
2(A6), 76(B7), 22(B8) |
| Yau 2019a [33] |
CheckMate 459 |
3 | Multi-centre |
• Randomized • Parallel Assignment • Open Label |
64.2 | 84.9 | NA | NA |
| Finn 2020 [41] | NCT03006926 | 1 | Multi-centre |
• NA • Single Group Assignment • Open Label |
66.5 | 81.0 | 29(B), 71(C) | 71(A5), 27(A6), 2(B7) |
| Finn 2020 [13] |
IMbrave 150 |
3 | Multi-centre |
• Randomized • Parallel Assignment • Open Label |
Atezo + Bev 64 SOR 66 |
Atezo + Bev 82 SOR 83 |
Atezo + Bev 2(A), 15(B), 82(C) SOR 4(A), 16(B), 81(C) |
Atezo + Bev 72(A5), 28(A6) SOR 73(A5), 27(A6) |
| Xu 2021 [42] |
RESCUE |
2 | Mainland China |
• NA • Single Group Assignment • Open Label |
1-L 53 2-L 51 |
1-L 90.0 2-L 88.3 |
1-L 17.1(B), 82.9(C) 2-L 18.3(B), 81.7(C) |
1-L 87.1(A5), 12.9(A6) 2-L 84.2(A5), 15.8(A6) |
| Kim 2021a [43] | NCT03347292 | 1b | United States |
• Non-Randomized • Sequential Assignment • Open Label |
67 | NA | 41(B), 55(C) | 100(A) |
| Jiao 2021a [44] | NCT04344158 | 3 | Mainland China |
• Randomized • Parallel Assignment • Open Label |
56 | NA | 23(B), 77(C) | NA |
| Kudo 2020a [45] |
Study 117 |
1b | Japan |
• Non-Randomized • Sequential A ssignment • Open Label |
NA | NA | NA | NA |
| Kudo 2020 [46] |
VEGF Liver 100 |
1 | Japan |
• Non-Randomized • Parallel Assignment • Open Label |
68.5 | 90.9 | 40.9(B), 59.1(C) | NA |
| Lee 2020 [35] |
GO30140 |
1b | Multi-centre |
• Randomized • Parallel Assignment • Open Label |
A 62 F1 60 F2 63 |
A 81 F1 90 F2 83 |
A 0(A), 10(B), 90(C) F1 0(A), 10(B), 90(C) F2 3(A), 7(B), 90(C) |
A 74(A5), 20(A6), 6(B7) F1 72(A5), 28(A6), 0(B7) F2 71(A5), 29(A6), 0(B7) |
| Li 2021 [52] | NCT03092895 | 1b/2 | Mainland China |
• Non-Randomized • Parallel Assignment • Open Label |
52 | 91.2 | 11.8(B), 85.3(C), 2.9(unknown) | 97.1(A), 2.9(B) |
| Lin 2021a [47] | ChiCTR1900028295 | 2 | Mainland China |
• NA • Single arm • Open Label |
NA | NA | NA | 100(≤ B7) |
| Ren 2021 [36] |
ORIENT-32 |
3 | Mainland China |
• Randomized • Parallel Assignment • Open Label |
Sintilimab + IBI305 53 SOR 54 |
Sintilimab + IBI305 88 SOR 90 |
Sintilimab + IBI305 15(B), 85(C) SOR 14(B), 86(C) |
Sintilimab + IBI305 96(A), 4(B) SOR 95(A), 5(B) |
| Kelley 2022 50] |
COSMIC-312 |
3 | Multi-centre |
• Randomized • Parallel Assignment • Open Label |
Cabozantinib + Atezo 64 SOR 64 |
Cabozantinib + Atezo 83 SOR 86 |
Cabozantinib + Atezo 32(B) 68(C) SOR 33(B) 67(C) |
Cabozantinib + Atezo 100(A) SOR 100(A) |
| He 2021a [53] | NCT04044313 | 2 | Mainland China |
• NA • Single Group Assignment • Open Label |
49 | 91.7 | NA | NA |
| Abou-Alfa 2022a [54] |
HIMALAYA |
3 | Multi-centre |
• Randomized • Parallel Assignment • Open Label |
NA | NA | NA | NA |
| Bai 2021a [48] | NCT04444167 | 2 | Mainland China |
• NA • Single Group Assignment • Open Label |
52.5 | 86.7 | NA | NA |
| Verset 2022 [34] |
KEYNOTE-224 |
2 | Multi-centre |
• NA • Single Group Assignment • Open Label |
68 | 86 | 22(B), 78(C) | 100(A) |
| Chen 2022 [51] | NCT04052152 | 2 | Mainland China |
• NA • Single Group Assignment • Open Label |
56 | 90.0 | 25(B), 75(C) | 95(A), 5(B) |
| Hao 2022a [37] | NCT04605796 | 2 | Mainland China |
• NA • Single Group Assignment • Open Label |
54 | 88.9 | 74.1(C) | NA |
| Meyer 2022a [38] | NCT03468426 | 1b | Multi-centre |
• NA • Single Group Assignment • Open Label |
1-L 65 2-L 64 |
1-L 87 2-L 77 |
NA | NA |
| Lim 2022a [39] | NCT02519348 | 2 | Multi-centre |
• Randomized • Parallel Assignment • Open Label |
NA | NA | NA | NA |
| Yoo 2022a [49] |
RENOBATE |
2 | Korea |
• NA • Single Group Assignment • Open Label |
61 (40–79) | 73.8 | 90.5(C) | NA |
| Maesaka 2022 [40] | NA | NA | Japan |
• NA • Parallel Assignment • Open Label |
Atezo + Bev 76 Len 73 |
Atezo + Bev 76.8 Len 76.3 |
Atezo + Bev 49.3(A/B), 50.7(C) Len 40.7(A/B), 50.3(C) |
Atezo + Bev 97.1(A), 2.9(B) Len 79.5(A), 20.5(B) |
| Author, year | Study drug(s), n | Comparator | Follow-up time (mo) | Outcome(s) studied | ||||
|---|---|---|---|---|---|---|---|---|
| PFS median, mo | OS median, mo | ORR (%) | DCR (%) | TRAEs (%) | ||||
| Kudo 2021 [32] | Nivo (SOR naïve), 25 | Nivo (SOR treated), 24 | 16.3 (12.2–22.5) |
1-L 3.4 (1.6–4.1) 2-L 2.2 (1.4–4.2) |
1-L 9.8 (3.7–14.3) 2-L 7.4 (2.3–12.1) |
1-L 12 2-L 13 |
1-L 60 2-L 50 |
Any grade: 1-L 44 2-L 58 |
| Yau 2019a [33] | Nivo, 371 | SOR, 372 | NA |
Nivo 3.68 (3.06–3.88) SOR 14.69 (11.89–17.22) |
Nivo 16.39 (13.93–18.37) SOR 14.69 (11.89–17.22) |
Nivo 15.4 SOR 7.0 |
NA |
SAEs: Nivo 56.40 SOR 58.95 |
| Finn 2020 [41] | Len + Pembro, 100 | NA | 10.6 (9.2–11.5) | 8.2 (7.4–9.7) | 22.0 (20.4-NE) | 46 | 86 | Grade ≥ 3 TRAEs: 67 |
| Finn 2020 [13] | Atezo + Bev, 336 | SOR, 165 |
Atezo + Bev 8.9 (7.1–11.1) SOR 8.1 (4.7–10.2) |
Atezo + Bev 6.83 (5.75–8.28) SOR 4.27 (3.98–5.55) |
Atezo + Bev NE SOR 13.2 (10.4-NE) |
Atezo + Bev 27.3 SOR 11.9 |
Atezo + Bev 73.6 SOR 55.3 |
Any grade: Atezo + Bev 98.2 SOR 98.7 |
| Xu 2021 [42] | Cam + Apa (1L), 70 | Cam + Apa (2L), 120 |
1-L 16.7 (11.1–18.2) 2-L 14.0 (9.6– 17.0) |
1-L 5.7 (5.4 -7.4) 2-L 5.5 (3.7–5.6) |
1-L NE 2-L NE |
1-L 34.3 2-L 22.5 |
1-L 77.1 2-L 75.8 |
1-L Grade ≥ 3: 78.6 2-L Grade ≥ 3: 76.7 |
| Kim 2021a [43] | Reg + Pembro, 29 | NA | NA | NA | NA | NA | NA | 24 |
| Jiao 2021a [44] | Penpulimab + Anlotinib, 31 | NA | 11.9 (3.7–17.7) | 7.6 | NE | 31 | 82.8 | Grade ≥ 3: 16.1 |
| Kudo 2020a [45] | Len + Nivo, 24 | NA | NA | NA | NA | 79.2 | NA | NA |
| Kudo 2020 [46] | Avelumab + axitinib, 22 | NA | NA | 5.52 (1.91–7.39) | 14.05 (7.95-NE) | 13.6 | 68.2 | Grade 3–4: 77.2 |
| Lee 2020 [35] | A: Atezo + Bev, 104 |
F1: Atezo + Bev, 60 F2: Bev, 59 |
A 6.6 (5.5–8.5) F1 6.6 (5.5–8.5) F2 6·7 (4.2–8.2) |
A 7.3 (5.4–9.9) F1 5.6 (3.6–7.4) F2 3.4 (1.9–5.2) |
A NE F1 NE F2 NE |
A 36 F1 20 F2 17 |
A 71 F1 67 F2 49 |
Grade 3–4: A 53 F1 17 F2 5 |
| Li 2021 [52] | Cam + FOLFOX4, 34 | NA | 11.5 (2.7–22.4) | 7.4 (3.9- 9.2) |
6 mo 79.4% 12 mo 50.0% |
29.4 | 79.4 | Grade ≥ 3 TRAEs: 85.3 |
| Lin 2021a [47] | Anlotinib + toripalimab, 30 | NA | NA | NA | NA | 25 | 87.5 | Grade 3: 45.5 |
| Ren 2021 [36] | Sintilimab + IBI305, 380 | SOR, 191 |
Sintilimab + IBI305 10.0 (8.5–11.7) SOR 10.0 (8.4–11.7) |
Sintilimab + IBI305 4.6 (4.1–5.7) SOR 2.8 (2.7–3.2) |
NA |
Sintilimab + IBI305 21 SOR 4 |
Sintilimab + IBI305 4.6 72 SOR 64 |
Grade ≥ 3: Sintilimab + IBI305 55 SOR 48.1 |
| Kelley 2022 [50] | Atezo + Cabozantinib, 432 |
SOR, 217, Cabozantinib, 188 |
15.8 (14.5–17.2) |
Cabozantinib + Atezo 6.8 (99% CI 5.6–8.3) SOR 4.2 (99% CI 2.8–7.0) |
Cabozantinib + Atezo 15.4 (96% CI 13.7–17.7) SOR 12.2 (96% CI 15.5-NE) |
Cabozantinib + Atezo 11 SOR 4 |
Cabozantinib + Atezo 78 SOR 65 |
Any grade: 93 |
| He 2021a [53] | Toripalimab + LEN + HAIC, 36 | NA | 11.2 | 10.5 (6.21 − 14.79) | NA | 63.9 | NA | Grade ≥ 3: 72.2 |
| Abou-Alfa 2022a [54] | Tremelimumab + durvalumab, 393 |
Durvalumab, 389, SOR, 389 |
STRIDE 16.1 Durvalumab 16.5 SOR 13.3 |
STRIDE 3.8 (3.7–5.3) Durvalumab 3.7 (3.2–3.8) SOR 4.1 (3.8–5.5) |
STRIDE 16.4 (14.2–19.6) Durvalumab 16.6 (14.1–19.1) SOR 13.8 (12.3–16.1) |
STRIDE 20.1 D 17.0 S 5.1 |
NA | Grade ≥ 3: 25.8 |
| Bai 2021a [48] | AK104 + LEN, 30 | NA | NA | NA | NA | 44.4 | 77.8 | Any grade: 83.3 |
| Verset 2022 [34] | Pembro, 51 | NA | 27 (range, 23–29) | 4 (2–8) | 17 (8–23) | 16 | 57 | Any grade: 55 |
| Chen 2021a [51] | Sintilimab + anlotinib, 20 | NA | 12 (range 3–19) | 12.2(3.8-NR) | NA | 40 | 95 | Any grade: 100 |
| Hao 2022a [37] | Toripalimab + Bev, 54 | NA | NA | 9.9 (5.5–11.0) | NE | 32.7 | 78.8 | Grade ≥ 3: 25.9 |
| Meyer 2022a [38] | Ezabenlimab + BI 836,880, 1-L 30 | Ezabenlimab + BI 836,880, 2-L 31 | NA | NA | NA | 21 | 85.7 | Any grade: 48 |
| Lim 2022a [39] | Durvalumab + Bev, 47 | NA | NA | NA | NE | 21.3 | NA | Any grade: 70.2 |
| Yoo 2022a [49] | Nivo + regorafenib, 42 | NA | 9.2 (8.5–9.9) | 5.5 (1.8–9.1) | NE | 31 | NA | NA |
| Maesaka 2022 [40] | Atezo + Bev, 69 | LEN, 161 | NA |
Atezo + Bev 8.8 LEN 5.2 |
Atezo + Bev NR LEN 20.6 |
Atezo + Bev 29.7 LEN 30.2 |
Atezo + Bev 71.9 LEN 82.5 |
Any grade: 98.5 |
1-L, first-line; 2-L, second-line; Atezo, atezolizumab; BCLC, Barcelona Clinic Liver Cancer; Bev, bevacizumab; Cam, camrelizumab; FOLFOX4, fluorouracil, leucovorin, and oxaliplatin; LEN, lenvatinib; mo, month; NA, not available; NE, not estimable; Nivo, nivolumab; Pembro, pembrolizumab; REG, regorafenib; SOR, sorafenib; SAEs, serious adverse events; STRIDE, tremelimumab plus durvalumab; TRAEs, treatment-related adverse events
aConference abstract