Immune Checkpoint Inhibitor Therapy Linked to Improved Survival in Unresectable HCC

Investigators compared the safety and efficacy of immune checkpoint inhibitors vs standard therapies for the treatment of unresectable hepatocellular carcinoma.

Immune checkpoint inhibitors (ICIs) are associated with significantly improved overall survival, progression-free survival, and overall response rate compared with standard therapies in patients with unresectable hepatocellular carcinoma (HCC), according to a study in JAMA Network Open.

The meta-analysis included randomized clinical trials (RCTs) regarding overall outcomes associated with use of ICIs compared with standard of care (sorafenib) in patients with unresectable HCC.

Researchers conducted a systematic literature search for studies published or presented between February 2010 and February 2020. Overall survival, progression-free survival, overall response rate, and grades 3 to 4 treatment-related adverse events (TRAEs) were the primary outcomes of interest.

The analysis included 3 phase 3 RCTs with 1657 patients — 985 received ICIs and 672 received standard care. Two studies compared first-line ICIs vs sorafenib and 1 study compared second-line ICI with placebo. The ICIs that were assessed were nivolumab, atezolizumab, and pembrolizumab.

Treatment with ICIs was associated with significant improvement in overall survival (hazard ratio [HR], 0.75; 95% CI, 0.62-0.92; P =.006), compared with standard care (sorafenib in first-line or placebo in second-line). ICIs were also associated with greater improvement in progression-free survival vs standard care (HR, 0.74; 95% CI, 0.56-0.97; P =.03).

According to use of the Response Evaluation Criteria in Solid Tumours (RECIST), treatment with ICIs was associated with greater overall response rate vs standard care (sorafenib in first-line or placebo in second-line) (odds ratio [OR] 2.82; 95% CI, 2.02-3.93; P <.001).

The overall probability of grade 3 or 4 TRAEs was lower among patients who received ICI treatment compared with those who received sorafenib (OR, 0.44; 95% CI, 0.20-0.96; P =.04).

The investigators noted that their findings are limited by the inclusion of only 3 studies.

“These findings suggest that ICIs should be the new standard of care in systemic therapy of unresectable HCC,” stated the researchers. “Several ongoing RCTs are addressing the role of combination therapies in the first-line and second-line settings, which offers promise for better outcomes in patients affected by such a severe disease.”

Disclosure: Some of the study authors declared affiliations with pharmaceutical companies. Please see the original reference for a full list of authors’ disclosures.


Jácome AA, Castro ACG, Vasconcelos JPS, et al. Efficacy and safety associated with immune checkpoint inhibitors in unresectable hepatocellular carcinoma: a meta-analysis. JAMA Netw Open. 2021;4(12):e2136128 doi: 10.1001/jamanetworkopen.2021.36128