Table 1.
Clinical biomarkers.
| Factor | Detail | Outcome | Regimen | Line of Treatment | Trial (Phase) | Ref. |
|---|---|---|---|---|---|---|
| Etiology | Hepatitis B | OS (HR 0.51) and PFS (HR 0.47) benefit | Atezolizumab + Bevacizumab vs. Sorafenib | 1st | IMbrae150 (III) | Finn et al. NEJM 2020 [19] |
| Hepatitis C | OS (HR 0.43) benefit | Atezolizumab + Bevacizumab vs. Sorafenib | 1st | IMbrae150 (III) | Finn et al. NEJM 2020 [19] | |
| Hepatitis B | OS (HR 0.64) benefit | Durvalumab + Tremelimumab vs. Sorafenib | 1st | Himalaya (III) | Abou-alfa et al. NEJM Evidence 2022 [20] | |
| Non-viral | OS (HR 0.74) benefit | Durvalumab + Tremelimumab vs. Sorafenib | 1st | Himalaya (III) | Abou-alfa et al. NEJM Evidence 2022 [20] | |
| HBV | OS (HR 0.57) benefit | Pembrolizumab vs. Placebo | 2nd | KEYNOTE-240 (III) | Finn et al. JCO 2019 [15] | |
| HBV | OS benefit | Nivolumab, Atezolizumab + Bevacizumab, Pembrolizumab (Meta-analysis) | 1st–2nd | CheckMate-459, IMbrave150 and KEYNOTE-240 (III) |
Pfister et al. Nature 2021 [16] | |
| HCV | OS benefit | Nivolumab, Atezolizumab + Bevacizumab, Pembrolizumab (Meta-analysis) | 1st–2nd | CheckMate-459, IMbrave150 and KEYNOTE-240 (III) |
Pfister et al. Nature 2021 [16] | |
| NAFLD | Worst survival | Nivolumab, Atezolizumab + Bevacizumab, Pembrolizumab (Meta-analysis) | 1st–2nd | CheckMate-459, IMbrave150 and KEYNOTE-240 (III) |
Pfister et al. Nature 2021 [16] | |
| BCLC stage | BCLC C (no benefit for BCLC B) | OS (HR 0.58) and PFS (HR 0.58) benefit | Atezolizumab + Bevacizumab vs. Sorafenib | 1st | IMbrae150 (III) | Finn et al. NEJM 2020 [19] |
| BCLC C (no benefit for BCLC B) | OS (HR 0.76) benefit | Durvalumab + Tremelimumab vs. Sorafenib | 1st | Himalaya (III) | Abou-alfa et al. NEJM Evidence 2022 [20] | |
| BCLC B and C | OS and PFS benefit | Sintilimab + bevacizumab biosimilar vs. Sorafenib | 1st | ORIENT-32 (III) | Ren et al. Lancet Oncol. 2021 [35] | |
| Extrahepatic Spread | Extrahepatic spread | OS (HR 0.5) benefit | Atezolizumab + Bevacizumab vs. Sorafenib | 1st | IMbrae150 (III) | Finn et al. NEJM 2020 [19] |
| Extrahepatic spread | OS (HR 0.67) benefit | Durvalumab + Tremelimumab vs. Sorafenib | 1st | Himalaya (III) | Abou-alfa et al. NEJM Evidence 2022 [20] | |
| Macrovascular invasion | Macrovascular invasion | OS (HR 0.58) benefit | Atezolizumab + Bevacizumab vs. Sorafenib | 1st | IMbrae150 (III) | Finn et al. NEJM 2020 [19] |
| No macrovascular invasion | OS (HR 0.77) benefit | Durvalumab + Tremelimumab vs. Sorafenib | 1st | Himalaya (III) | Abou-alfa et al. NEJM Evidence 2022 [20] | |
| Tumor Marker | AFP < 400ng/mL | OS (HR 0.52) and PFS (0.49) benefit | Atezolizumab + Bevacizumab vs. Sorafenib | 1st | IMbrae150 (III) | Finn et al. NEJM 2020 [19] |
| AFP ≥ 400ng/mL | OS (HR 0.64) benefit | Durvalumab + Tremelimumab vs. Sorafenib | 1st | Himalaya (III) | Abou-alfa et al. NEJM Evidence 2022 [20] | |
| AFP ≥ 400ng/mL | OS benefit | Nivolumab vs. Sorafenib | 1st | CheckMate-459 (III) | Yau et al. Lancet Oncol. 2022 [14] | |
| AFP < 400ng/mL | OS benefit | Nivolumab | 1st–2nd | CheckMate-040 (I/II) | Sangro et al. J. Hep. 2020 [61] | |
| AFP < 200ng/mL | OS (HR 0.68) and PFS (HR 0.64) benefit | Pembrolizumab vs. Placebo | 2nd | KEYNOTE-240 (III) | Finn et al. JCO 2019 [15] | |
| Other laboratory tests | Neutrophil-to-lymphocyte ratio | OS benefit for pts with low tertile | Nivolumab | 1st–2nd | CheckMate-040 (I/II) | Sangro et al. J. Hep. 2020 [61] |
| Platelet-to-lymphocyte ratio | OS benefit for pts with low tertile | Nivolumab | 1st–2nd | CheckMate-040 (I/II) | Sangro et al. J. Hep. 2020 [61] | |
| PD-L1 IHC | PD-L1 TC (28-8) ≥ 1% | No significant benefit | Nivolumab vs. Sorafenib | 1st | CheckMate-459 (III) | Yau et al. Lancet Oncol. 2022 [14] |
| PD-L1 TC (28-8) ≥ 1% | ORR (28% vs. 16%) and OS (28.1 vs. 16.6 months, p = 0.032) benefit |
Nivolumab | 1st–2nd | CheckMate-040 (I/II) | El-Khoueiry et al. Lancet 2017 [12] | |
| PD-L1 CPS (22C3) ≥ 1% | ORR (32% vs. 20%, p = 0.021) benefit | Pembrolizumab | 2nd | KEYNOTE-224 (II) | Zhu et al. Lancet Oncol. 2018 [13] | |
| PD-L1 TPS (SP142) ≥ 1% | ORR 36% vs. 11% | Camrelizumab | 2nd | NCT02989922 (II) | Qin et al. Lancet Oncol. 2020 [14] | |
| PD-L1 TC or IC (SP263) ≥ 1% | PFS (OR 2.69) benefit | Atezolizumab + Bevacizumab vs. Sorafenib | 1st | IMbrae150 (III) | Cheng et al. J. Hepatol. 2022 [58] |