Table 1 The PD-L1 expression as the biomarker in the advanced hepatocellular carcinoma clinical trials of immunotherapy

CheckMate 040

(El-Khoueiry et al., 2017) [5]

Nivolumab

Interventional; N = 218; 1st and more (Sorafenib progressor or Sorafenib untreated or intolerant)

Escalation phase: 11 vs. 33; Expansion phase: 34 vs. 140

(Dako 28 − 8) TC ≥ 1%

Escalation phase: ORR (27% vs. 12%)

Expansion phase: ORR (26% vs. 19%)

CheckMate 040

(Yau et al., 2020) [17]

Nivolumab plus ipilimumab

Interventional; N = 145^†; 2nd

Arm A: 10 vs. 39; Arm B:10 vs. 38; Arm C: 8 vs. 40

(Dako 28 − 8) TC ≥ 1%

ORR (Arm A:30% vs. 31%; Arm B:30% vs. 32%; Arm C:50% vs. 28%)

Check Mate 459

(Yau et al., 2022) [14]

Nivolumab

Interventional; N = 366; 1st

71 vs. 295

(Dako 28 − 8) TC ≥ 1%;

ORR (28% vs. 12%)

Median PFS (3.8 vs. 3.6 months)

Median OS (16.1 vs. 16.7 months)

Keynote-224

(Zhu et al., 2018) [6]

Pembrolizumab

Interventional; N = 52; 2nd

CPS: 22 vs. 30

(Dako 22C3) CPS ≥ 1

ORR (32% vs. 20%)

TPS: 7 vs. 45

(Dako 22C3) TPS ≥ 1%

ORR (43% vs. 22%)

GO30140

(Lee et al., 2020) [15]

Atezolizumab plus bevacizumab

Interventional; N = 86; 1st

1% cutoff: 61 vs. 25;

5% cutoff: 37 vs. 49;

10% cutoff: 30 vs. 56

(Ventana SP263) TC or IC ≥ 1%

ORR (41% vs. 28%)

(Ventana SP263) TC or IC ≥ 5%

ORR (41% vs. 31%)

(Ventana SP263) TC or IC ≥ 10%

ORR (50% vs. 30%)

NCT02989922

(Qin et al., 2020) [16]

Camrelizumab

Interventional; N = 30; 2nd

11 vs. 19

(Ventana SP142) TPS ≥ 1%

ORR (36% vs. 11%)

NCT03389126

(Lee et al., 2020) [18]

Avelumab

Interventional; N = 27; 2nd

22C3:6 vs. 21; SP263:8 vs. 19; SP142: 14 vs. 13; E1L3N: 10 vs. 17; PD-1 positive: 11 vs. 16

(Dako 22C3) TPS ≥ 1%

ORR (0.0% vs. 14.3%, P = 1.00); DCR (50.0% vs. 85.7%, P = 0.10)

(Ventana SP263) TPS ≥ 1%

ORR (12.5% vs. 10.5%), P = 1.00); DCR (75.0% vs. 78.9%, P = 1.00)

(Ventana SP142) IC ≥ 1%

ORR (21.4% vs. 0.0%, P = 0.22); DCR (71.4% vs. 84.6%, P = 0.65)

(Cell Signalling E1L3N) score ≥ 1

ORR (20.0% vs. 5.9%, P = 0.54); DCR (60.0% vs. 88.2%, P = 0.15)

PD-1 positive

ORR (18.2% vs. 6.2%, P = 0.55); DCR (81.8% vs. 75%, P = 1.00)

Imbrave150

(Cheng et al., 2022)

[107]

Atezolizumab + Bevacizumab vs. Sorafenib

Interventional; N = 135; 1st

86 vs. 49

(Ventana SP263) TC or IC ≥ 1%

Median OS (22.8 (17.0-NE) vs.19.9 (13.9-NE)); Median PFS (7.0 (5.6–9.9) vs. 6.7 (5.4–10.0)); ORR (36% vs. 27%)

HIMALAYA

(Abou-Alfa et al., 2022)

[19]

STRIDE vs. Sorafenib

Durvalumab vs. Sorafenib

Interventional; N = 681; 1st

STRIDE group:148 vs. 189; Durvalumab group:154 vs. 190

(Ventana SP263) TAP ≥ 1%

9-month OS rate: 68.2% vs. 67.7% (STRIDE group)

9-month OS rate: 69.5% vs. 74.2% (Durvalumab group)