Efficacy and safety of the immune checkpoint inhibitor-radiotherapy combination in advanced/unresectable hepatocellular carcinoma: A systematic review and meta-analysis.

Limited treatment options are available for patients with advanced stages of hepatocellular carcinoma (HCC), which is a major global health challenge. The present systematic review and meta-analysis examined the therapeutic potential of the combination of immune checkpoint inhibitors (ICIs) and radiotherapy (RT) for advanced (a)HCC or unresectable HCC. The PubMed, Embase, Cochrane Library and Web of Science databases were searched to identify studies examining the therapeutic efficacy of the ICI-RT combination for aHCC published until August 31, 2024. The following clinical outcomes were analyzed: Objective response rate (ORR), median progression-free survival (mPFS) and median overall survival (mOS). Additionally, targeted subgroup analyses were performed based on tumor thrombus presence and the use of transarterial chemoembolization (TACE) and stereotactic body RT. The present single-arm meta-analysis, encompassing 16 studies involving 633 patients with aHCC or unresectable HCC, revealed that the ICI-RT combination exhibits potent therapeutic efficacy. The pooled ORR of patients in the ICI-RT combination group was 54.4% [95% confidence interval (CI), 46.8-62.0%]. The mPFS and mOS of patients treated with the ICI-RT combination were 10.1 (95% CI, 7.2-12.9) and 18.3 months (95% CI, 14.6-21.9), respectively. The ORR of patients in the TACE combination subgroup was 53.8% (95% CI, 44.6-62.9%). Meanwhile, the ORR and mOS of patients with Barcelona Clinic Liver Cancer stage C tumors were 55.6% (95% CI, 44.3-66.9%) and 21.2 months (95% CI, 13.5-29.0), respectively. These findings suggest that ICI and RT exert synergistic effects. The ICI-RT combination, a promising therapeutic regime for aHCC, is associated with potent efficacy and favorable ORR and survival outcomes. Further studies are needed to optimize treatment strategies and identify patient subgroups who can benefit from this approach. The findings of the present study contribute to advances in aHCC treatment. The protocol for the present systematic review was registered at PROSPERO (registration no. CRD42024583148) and is available in full on the Health Technology Assessment website of the National Institutes of Health (http://www.hta.ac.uk/2283).