SYSTEMATIC REVIEW article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1573505
This article is part of the Research TopicImmunology and Therapeutic Innovations in Hepatocellular Carcinoma: Exploring Immune Evasion and BeyondView all articles
The impact of immune checkpoint inhibitors on prognosis in unresectable hepatocellular carcinoma treated with TACE and lenvatinib: A meta-analysis
Provisionally accepted
- Cancer Hospital Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China
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Background Combination of multiple therapies is a common approach to treating patients with unresectable hepatocellular carcinoma(uHCC). The impact of immune checkpoint inhibitors (ICIs) on prognosis in uHCC patients treated with transarterial chemoembolization (TACE) and lenvatinib remains unclear.Aim The purpose of this study was to compare the efficacy and safety of TACE plus lenvatinib plus ICIs(TACE+L+I) with TACE plus lenvatinib (TACE+L) in the treatment of patients with uHCC.Methods Publicly available studies comparing the efficacy and safety of TACE+L+I and TACE+L in the treatment of uHCC were collected from the databases PubMed, Embase and Cochrane Library, with a cut-off date of November 1, 2024. Stata SE 15 software was used for analysis.Results Fifteen studies with a total of 1365 patients were included, 688 in the TACE+L+I group and 677 in the TACE+L group. Meta-analysis showed that the TACE+L+I group was significantly higher than the TACE+L group in complete response (RR = 2.34, 95%CI:1.53, 3.59, p < 0.0001), partial response (RR = 1.45, 95%CI:1.28, 1.64, p < 0.0001), objective response rate (RR = 1.55, 95%CI:1.39, 1.73, p < 0.00001), and disease control rate (RR = 1.22, 95%CI:1.10, 1.36, p = 0.0003). The TACE+L+I group was significantly lower than the TACE+L group in progression of disease (RR = 0.39, 95%CI:0.30, 0.51, p < 0.00001). Moreover, TACE+L+I group was not significantly different from TACE+L group in stable disease (RR = 0.85, 95%CI:0.69, 1.03, p = 0.10). The TACE+L+I group was significantly higher than the TACE+L group in overall survival (HR = 2.32, 95%CI:1.95, 3.15, p<0.05) and progression-free survival (HR = 2.30, 95%CI:1.80, 2.93, p<0.05). The TACE+L+I group had a significantly higher incidence of hypothyroidism compared to the TACE+L group (RR = 1.81, 95%CI:1.20, 2.71, p<0.05), but there was no significant difference in other adverse events, such as hypertension, diarrhea, hand-foot syndrome, fatigue, elevated AST, elevated ALT, decreased appetite, hypothyroidism, abdominal pain, thrombocytopenia, rash, and nausea.Conclusion ICIs significantly improved the survival outcome of uHCC treated with TACE+L, and increased the incidence of hypothyroidism. However, this conclusion still needs further validation in the future with more high-quality randomized controlled trials and longer follow-up.
Keywords: Hepatocellular Carcinoma, Transarterial chemoembolization, Lenvatinib, Immune checkpoint inhibitor, PD-1 inhibitor, combined therapy
Received: 09 Feb 2025; Accepted: 25 Apr 2025.
Copyright: © 2025 Zhang, Liu, Liu, Huang, Huang, Xu, Zhan and Che. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Xu Che, Cancer Hospital Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China
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