International journal of surgery (London, England) · 2025
Comparative efficacy and safety of immune checkpoint inhibitors-based strategies in advanced hepatocellular carcinoma: a systematic review and network meta-analysis.
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Yu Xinlin, Zhang Xialin, Jiang Ou, Li Xinwei, Chen Gang, Li Xingming, Xu Yanneng, Lin Sheng, Yuan Gang, Cui Ran
Аннотация
ABSTRACT: Given the aggressive nature and high mortality associated with advanced hepatocellular carcinoma (HCC), optimizing the selection of immune checkpoint inhibitor (ICI) regimens is crucial for enhancing patient outcomes. Currently, the comparative efficacy and safety profiles of ICI-based therapies for advanced HCC are not well-defined, and there is a lack of systematic analyses to guide personalized treatment decisions.
OBJECTIVE: To conduct a systematic review and network meta-analysis (NMA)to determine the efficacy characteristics and safety level of ICIs-based combination therapy for advanced HCC.
METHODS: Relevant English-language articles published from January 2000 to May 2025 were systematically searched and analyzed, including PubMed, Embase, the Cochrane Library, and Web of Science. Randomized clinical trials or cohort studies that investigated the efficacy or safety of ICIs-based combinations with other treatments for advanced HCC were included. Objective response rate (ORR), median progression-free survival (mPFS), and median overall survival (mOS) are primary indicators of efficacy, whereas treatment-related adverse events (trAEs) are the primary safety indicator.
RESULTS: Across 41 studies (n = 16,008),efficacy analysis revealed that the toripalimab-based combination had the highest survival outcome [mPFS: 9.6 months (95% CI, 8.3-11.0); mOS: 17.1 months (95% CI, 14.0-20.0)], and the ICIs + hepatic artery infusion chemotherapy (HAIC) + TKI combination provided an optimal survival benefit [mPFS: 10.8 months (95% CI 9.61-11.60); mOS: 21.1 months (95% CI, 15.0-27.2)]. Safety analysis revealed that atezolizumab-based combination had the lowest severe trAEs (grade 3-4 trAEs, SUCRA = 26.8%), whereas immunotherapy as initial treatment markedly reduced toxicity compared with other sequencing strategies (grade 3-4 trAEs, SUCRA = 12.9% vs. 46.4%). Programmed cell death protein 1 (PD-1) inhibitors showed greater efficacy but slightly greater toxicity than programmed cell death-ligand 1 (PD-L1) inhibitors did (ORR SUCRA = 99.1% vs. 49.7%; grade 3-4 trAEs: 44.5% vs. 43.6%).
CONCLUSIONS: This systematic review and NWA reveals substantial heterogeneity in efficacy and safety profiles among ICIs-based combinations for advanced HCC. These findings support individualized treatment selection matching patient profiles with regimen-specific risk-benefit patterns, with toxicity monitoring to optimize outcomes.
OBJECTIVE: To conduct a systematic review and network meta-analysis (NMA)to determine the efficacy characteristics and safety level of ICIs-based combination therapy for advanced HCC.
METHODS: Relevant English-language articles published from January 2000 to May 2025 were systematically searched and analyzed, including PubMed, Embase, the Cochrane Library, and Web of Science. Randomized clinical trials or cohort studies that investigated the efficacy or safety of ICIs-based combinations with other treatments for advanced HCC were included. Objective response rate (ORR), median progression-free survival (mPFS), and median overall survival (mOS) are primary indicators of efficacy, whereas treatment-related adverse events (trAEs) are the primary safety indicator.
RESULTS: Across 41 studies (n = 16,008),efficacy analysis revealed that the toripalimab-based combination had the highest survival outcome [mPFS: 9.6 months (95% CI, 8.3-11.0); mOS: 17.1 months (95% CI, 14.0-20.0)], and the ICIs + hepatic artery infusion chemotherapy (HAIC) + TKI combination provided an optimal survival benefit [mPFS: 10.8 months (95% CI 9.61-11.60); mOS: 21.1 months (95% CI, 15.0-27.2)]. Safety analysis revealed that atezolizumab-based combination had the lowest severe trAEs (grade 3-4 trAEs, SUCRA = 26.8%), whereas immunotherapy as initial treatment markedly reduced toxicity compared with other sequencing strategies (grade 3-4 trAEs, SUCRA = 12.9% vs. 46.4%). Programmed cell death protein 1 (PD-1) inhibitors showed greater efficacy but slightly greater toxicity than programmed cell death-ligand 1 (PD-L1) inhibitors did (ORR SUCRA = 99.1% vs. 49.7%; grade 3-4 trAEs: 44.5% vs. 43.6%).
CONCLUSIONS: This systematic review and NWA reveals substantial heterogeneity in efficacy and safety profiles among ICIs-based combinations for advanced HCC. These findings support individualized treatment selection matching patient profiles with regimen-specific risk-benefit patterns, with toxicity monitoring to optimize outcomes.