Immune checkpoint inhibitors (ICIs) may be safer than tyrosine kinase inhibitors (TKIs) as neoadjuvant therapy for patients with advanced hepatocellular carcinoma (HCC), according to a meta-analysis published in JAMA Network Open

Researchers found lower rates of serious and severe adverse events (AEs) with ICIs than with TKIs. However, rates of liver toxicity were similar with the 2 treatment types.

The researchers conducted this meta-analysis to evaluate current evidence on AE profiles of treatments for advanced HCC, with a particular focus on designing clinicals trials for neoadjuvant treatment.

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The analysis included data from 30 single-group, placebo-controlled, and dual-agent phase 2 and 3 trials. The trials encompassed 12,921 patients with advanced HCC. 

The researchers found that severe AEs occurred in 46% of patients receiving a TKI, 24% of patients receiving an ICI, and 36% of patients receiving both an ICI and a TKI. 

Grade 3 or higher AEs occurred in 69% of patients receiving a TKI, 35% of those receiving an ICI, and 67% of those receiving both. Liver AEs were observed in 21% of patients receiving a TKI and 28% of those receiving an ICI. 

The researchers also compared sorafenib with other TKIs and found a similar risk of liver AEs between the groups (risk ratio [RR], 1.06; 95% CI, 0.92-1.24) but a higher risk of severe AEs with the other TKIs (RR, 1.24; 95% CI, 1.07-1.44). 

When the researchers compared ICIs with sorafenib, they found a similar risk of liver AEs (RR, 1.10; 95% CI, 0.86-1.40) and severe AEs between the groups (RR, 1.19; 95% CI, 0.95-1.50).

“In this study, ICIs had a more favorable toxicity profile than TKIs among patients with advanced HCC and therefore may be the more appropriate agent in the neoadjuvant setting,” the researchers concluded.

Disclosures: One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Griffiths CD, Zhang B, Tywonek K, Meyers BM, Serrano PE. Toxicity profiles of systemic therapies for advanced hepatocellular carcinoma. A systematic review and meta-analysis. JAMA Network Open. Oncol. Published online July 18, 2022. doi:10.1001/jamanetworkopen.2022.22721