The effectiveness and safety of immune checkpoint inhibitors in conversion or neoadjuvant therapy for hepatocellular carcinoma: a meta-analysis and systematic review

The adoption of immune checkpoint inhibitors in combination with tyrosine kinase inhibitors (TKIs) and/or local therapy, including transarterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC), has been utilized as neoadjuvant or conversion therapy for hepatocellular carcinoma. However, the efficacy of different combinations in terms of conversion or neoadjuvant therapy varies. We conducted a single-group rate meta-analysis to determine the conversion rate or resection rate, tumor response, and corresponding 95% confidence intervals (CI) for the therapeutic combinations. The tumor response and adverse events were also evaluated. The prognosis of patients receiving neoadjuvant therapy followed by surgery and surgery alone was also compared by evaluating HR and its 95%CI. Forty-nine studies were included, with thirty-six studies involving 3497 patients focusing on conversion therapy and the remaining thirteen involving 569 patients focusing on neoadjuvant therapy. The meta-analysis revealed a conversion rate of 0.23 (95% CI: 0.18–0.29). Subgroup analyses based on different treatments revealed a conversion rate of patients receiving is the combination of ICIs, TKIs, and TACE or HAIC about 30%, while the conversion rate of patients receiving T + A is about 4%. When evaluated by modified Response Evaluation Criteria In Solid Tumors (mRECIST), the objective response rate (ORR) is 0.62 (95% CI: 0.56–0.67), the disease control rate is 0.87 (95% CI: 0.84–0.90). The incidence of adverse events (AEs) and severe AEs is 0.95 (95% CI: 0.92–0.98) and 0.39 (95% CI: 0.32–0.46), respectively. The meta-analysis revealed a resection rate of 0.87 (95% CI: 0.85–0.90). The OS and RFS of patients receiving neoadjuvant therapy followed by surgery is similar to those receiving surgery alone. Our study provides a comprehensive summary of the current evidence regarding the success rates of conversion therapy, including comparisons between different treatment regimens and associated adverse effects. Additionally, we present findings on the role and side effects of neoadjuvant therapy in resectable HCC.