Efficacy and safety of adjuvant targeted immunotherapy for hepatocellular carcinoma with high recurrence risks after hepatectomy

Abstract

BACKGROUND

Postoperative recurrence of hepatocellular carcinoma (HCC) is an important factor affecting long-term patient survival, and there is a lack of effective methods to reduce the chance of recurrence and metastasis after hepatectomy.

AIM

To study the efficacy and safety of targeted and/or immunotherapy for HCC with high recurrence risks after hepatectomy, and to explore the target population that would benefit from receiving adjuvant therapy after hepatectomy.

METHODS

A retrospective analysis of 1708 patients for hepatic resection for HCC from January 2019 to August 2022. According to whether or not they received postoperative immunotherapy and/or molecular-targeted therapy, they were divided into the adjuvant therapy group and the surgery-only group. The primary study endpoint was relapse-free survival, and secondary outcomes were overall survival (OS) and treatment-related adverse events. Cox analyzes were applied to find risk factors affecting recurrence-free survival. Subgroup analyzes were performed to further compare the targeted therapy, immunotherapy and targeted therapy combined with immunotherapy groups in the adjuvant therapy group in order to explore the safety and efficacy of adjuvant therapy.

RESULTS

Postoperative tumor recurrence was observed in 230 cases (61.8%), of which 122 cases (32.7%) had tumor recurrence within one year after surgery. The OS rate was 95.9% (357/372). Analysis of prognosis yielded a statistically significant difference in recurrence free survival (RFS) between the two groups (median RFS, 26.0 months vs 14.0 months, P = 0.028), while OS was not statistically significant (P = 0.620). Multifactorial Cox regression analysis in the entire cohort identified independent prognostic factors for RFS including receipt of adjuvant therapy (P = 0.005, hazard ratio = 0.657) and maximum tumor diameter (P = 0.039, hazard ratio = 1.006). In the subgroup analysis, the targeted therapy group had the highest 1-year RFS rate (88.6%) among all subgroups. In terms of safety, the most common adverse reactions were elevated alanine aminotransferase/aspartate aminotransferase (28.41%), hypertension (26.13%), rash or dermatitis (25.00%), and diarrhea (22.73%), and there were 4 cases of grade 3-4 adverse reactions (4.55%), and most of the adverse reactions were reversible.

CONCLUSION

Targeted and/or immunotherapy has shown better efficacy and safety in HCC patients at high risk of recurrence after hepatectomy.

Keywords: Hepatocellular carcinoma; Hepatectomy; Recurrence; Adjuvant therapy; Tyrosine kinase inhibitors; Immune-checkpoint inhibitors; Cohort study

Core Tip: This retrospective cohort study demonstrates that adjuvant targeted and/or immunotherapy can significantly improve recurrence-free survival in hepatocellular carcinoma patients at high risk of recurrence after hepatectomy, compared to surgery alone. The therapy was identified as an independent protective factor against recurrence. While a clear overall survival benefit was not observed in this analysis, the treatment regimen showed a manageable safety profile, with most adverse events being reversible. These findings support the potential role of this adjuvant strategy in improving outcomes for this patient population.