Systemic treatment of liver cancer: Current status and future perspectives

Table 3 Comparison of core mechanisms of three immunotherapy drugs

Drug	Target of action	Mechanism of action	Main indications	Key clinical data	Common adverse reactions
Pembrolizumab	PD-1	Block the binding of PD-1 to its ligands PD-L1/PD-L2, relieve the immunosuppression of T cells, activate tumor-specific T cells, enhance the ability of the immune system to attack tumors, and restore the immune surveillance function through the inhibition of immune checkpoints	Melanoma, non-small cell lung cancer, head and neck cancer, gastric cancer, liver cancer, etc.	KEYNOTE-394: The median OS with pembrolizumab was 14.6 months, the 2-year OS rate reached 34.3%	Immune-related adverse reactions (pneumonia, colitis, thyroiditis), fatigue, skin rash
Nivolumab	PD-1	It binds to PD-1, blocks the PD-L1/PD-L2 signaling pathway, enhances the proliferation of T cells and the release of cytokines. When combined with CTLA-4 inhibitors, it can synergistically enhance the anti-tumor effect	Melanoma, non-small cell lung cancer, gastric cancer, renal cancer, etc.	CheckMate-040: The objective response rate (ORR) in the dose escalation cohort: 15%. ATTRACTION-4: The median OS for gastric cancer patients is 26.6 months	Immune-mediated pneumonia, hepatitis, endocrine diseases, infusion reactions
Ramucirumab	VEGFR2	It specifically binds to VEGFR2, inhibits VEGF-A-mediated angiogenesis, reduces the blood supply to tumors, and suppresses tumor growth and metastasis	Gastric cancer, liver cancer, non-small cell lung cancer, colorectal cancer	REACH-2 trial: The median overall survival for liver cancer patients with AFP ≥ 400 ng/mL is 8.5 months (compared with 7.3 months for the placebo group)	Hypertension, proteinuria, bleeding risk, gastrointestinal reactions

PD-1: Programmed cell death protein 1; PD-L1: Programmed death-ligand 1; PD-L2: Programmed death-ligand 2; OS: Overall survival; ORR: Objective response rate; CTLA-4: Cytotoxic T-lymphocyte-associated protein 4; VEGFR2: Vascular endothelial growth factor receptor 2; AFP: Alpha-fetoprotein.