Non-alcoholic fatty liver disease-related hepatocellular carcinoma: Is there a role for immunotherapy?

Table 1 Summary of randomized controlled trials on systemic therapy for advanced hepatocellular carcinoma

Ref.	Interventions	Mechanisms of action	Main results
Llovet et al[57]	Sorafenib × placebo	TKI × placebo	Increased OS with sorafenib
Cheng et al[56]	Sorafenib × placebo	TKI × placebo	Increased OS with sorafenib
Bruix1 et al[59]	Regorafenib × placebo	TKI × placebo	Increased OS with regorafenib
Kudo et al[61]	Lenvatinib × sorafenib	TKI × TKI	Non-inferior OS
Abou-Alfa2 et al[58]	Cabozantinib × placebo	TKI × placebo	Increased OS with cabozantinib
Zhu1,3 et al[60]	Ramucirumab × placebo	Anti-VEGF receptor 2 × placebo	Increased OS with ramucirumab
Yau et al[73]	Nivolumab × sorafenib	Anti-PD-1 × TKI	No increase in OS4
Finn1 et al[74]	Pembrolizumab × placebo	Anti-PD-L1 × placebo	No increase in OS4
Finn et al[19]	Atezolizumab + bevacizumab × sorafenib	Anti-PD-L1 + anti-VEGF × TKI	Increased OS with atezolizumab + bevacizumab
Kelley et al[79]	Atezolizumab + cabozantinib × sorafenib × cabozantinib	Anti-PD-L1 + TKI × TKI × TKI	No increase in OS4
Abou-Alfa et al[82]	Tremelimumab + durvalumab × durvalumab × sorafenib	Anti-CTLA-4 + anti-PD-L1 × anti-PD-L1 × TKI	Increased OS with tremelimumab + durvalumab (× sorafenib). Non-inferior OS with durvalumab (× sorafenib)

¹2^nd line treatment.

²2^nd or 3^rd line treatment.

³Individuals with alpha-fetoprotein ≥ 400 ng/mL.

⁴Primary endpoint not reached.

TKI: Tyrosine kinase inhibitor; OS: Overall survival; VEGF: Vascular endothelial growth factor; PD-1: Programmed cell death protein 1; PD-L1: Programmed cell death ligand-1; CTLA-4: Cytotoxic T-lymphocyte-associated protein 4.