Review
Copyright ©The Author(s) 2022.
World J Gastrointest Oncol. Sep 15, 2022; 14(9): 1622-1636
Published online Sep 15, 2022. doi: 10.4251/wjgo.v14.i9.1622
Table 1 The main immune checkpoint inhibitors approved for treatment of advanced hepatocellular carcinoma
Drug
Mechanism of action
Efficacy
Safety
Approval
First-line
Atezolizumab (1200 mg, IV) plus bevacizumab (15 mg/kg, IV) every 3 wkICI, anti-PD-L1 antibody (atezolizumab) plus antiangiogenic, anti-VEGF-A antibody (bevacizumab)Improved OS, PFS, ORR vs sorafenib (IMbrave-150 phase III trial[93])irAEs1, hypertension, fatigue, proteinuria, pruritus, gastrointestinal bleedingApproved by FDA and EMA for patients with advanced HCC
Tremelimumab (300 mg, IV) plus durvalumab (1500 mg, IV) once, followed by durvalumab (1500 mg, IV) every 4 wkICI, anti-CTLA-4 antibody (tremelimumab) plus ICI, anti-PD-L1 antibody (durvalumab)Improved OS vs sorafenib and favorable benefit-risk ratio (HIMALAYA phase III trial[89])Pruritus, irAEs1Under evaluation for approval. Granted orphan drug designation by FDA for HCC treatment (2020)
Sintilimab (200 mg, IV) plus IBI305 (bevacizumb biosimilar; 15 mg/kg, IV) every 3 wkICI, anti-PD-1 antibody (sintilimab) plus antiangiogenic, anti-VEGF-A antibody (IBI305)Better OS and PFS in HBV-related advanced HCC vs sorafenib (ORIENT-32 phase II/III trial[113])Proteinuria, irAEs1, thrombocytopenia, leukopenia, hypertension, fatigueApproved by NMPA in China for patients with advanced HCC (2021)
Second-line
pembrolizumab (200 mg, IV) every 3 wk plus best supportive careICI, anti-PD-1 monoclonal antibodyBetter OS, PFS and ORR in patients post-sorafenib vs placebo (KEYNOTE-394 phase III trial[114] and KEYNOTE-224 phase II trial[115])irAEs1, fatigue, pruritus, anorexiaApproved by FDA for advanced HCC post-sorafenib (2018)
Nivolumab (1 mg/kg, IV) plus ipilimumab (3 mg/kg, IV) every 3 wk for 4 cycles, followed by nivolumab (240 mg, IV) every 2 wkICI, anti-PD-1 monoclonal antibody (nivolumab) plus ICI, anti-CTLA-4 antibody (ipilimumab)Promising OS and durable response post-sorafenib (cohort 4 of CheckMate-040 phase I/II trial[90]). CheckMate 9DW phase III trial ongoing[116]Pruritus, irAEs1Approval by FDA for advanced HCC post-sorafenib (2020)