Efficacy and Safety of Adjuvant Immune Checkpoint Inhibitors in Hepatocellular Carcinoma Post-Reception: A Meta-analysis

Abstract

Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide. Although curative treatments such as surgical resection and liver transplantation offer potential for long-term survival, recurrence remains a significant challenge. Immune checkpoint inhibitors (ICIs), including nivolumab, pembrolizumab, atezolizumab, and sintilimab, have demonstrated efficacy in advanced HCC, yet their role in the adjuvant setting remains inadequately defined. Objective: This meta-analysis evaluates the efficacy and safety of adjuvant ICIs in enhancing overall survival (OS) and recurrence-free survival (RFS) in HCC patients following curative resection or ablation. Methods: We conducted a systematic review of randomized controlled trials (RCTs) published between 2019 and 2024, which assessed the use of adjuvant ICIs in post-resection HCC. A total of 10 studies were included in the final analysis. Pooled hazard ratios (HRs) for OS and RFS, along with adverse event rates, were calculated using a random-effects model. Subgroup analyses were performed based on tumor stage, ICI regimen, and geographic region. Publication bias was assessed using funnel plots, and Egger’s test was conducted. Results: Adjuvant ICI therapy significantly improved RFS with a pooled HR of 0.534 (95% CI: 0.360–0.792), indicating a 46.6% reduction in the risk of recurrence compared to placebo or standard care. The pooled HR for OS was 0.85 (95% CI: 0.72–1.02), suggesting a trend toward improved survival, although this did not reach statistical significance. Common grade 3+ adverse events included fatigue, hypertension, and elevated liver enzymes. Conclusion: Adjuvant ICIs represent a promising therapeutic strategy for post-resection HCC, offering improvements in RFS with a manageable toxicity profile. However, further long-term trials are required to confirm the sustained benefits and establish the role of ICIs in clinical practice.