The efficacy and safety of immune combination therapy in patients with driver gene-negative non-small cell lung cancer with liver metastasis: a systematic review and network meta-analysis

Abstract Objective This study aimed to systematically evaluate the efficacy and safety of combination therapies with immune checkpoint inhibitors (ICIs) in patients with driver gene-negative non-small cell lung cancer (NSCLC) and liver metastases. These patients typically have poor prognosis and lim...

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Main Authors: Weixing Zhao, Bo Li, Yujia Gu, Xiaoni Jin, Zirui Li, Wanjing Guo, Xinxin Lu, Jun Jiang
Format: Article
Language:English
Published: BMC 2025-08-01
Series:BMC Cancer
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Online Access:https://doi.org/10.1186/s12885-025-14712-w
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author Weixing Zhao
Bo Li
Yujia Gu
Xiaoni Jin
Zirui Li
Wanjing Guo
Xinxin Lu
Jun Jiang
author_facet Weixing Zhao
Bo Li
Yujia Gu
Xiaoni Jin
Zirui Li
Wanjing Guo
Xinxin Lu
Jun Jiang
author_sort Weixing Zhao
collection DOAJ
description Abstract Objective This study aimed to systematically evaluate the efficacy and safety of combination therapies with immune checkpoint inhibitors (ICIs) in patients with driver gene-negative non-small cell lung cancer (NSCLC) and liver metastases. These patients typically have poor prognosis and limited responses to immunotherapy. This study synthesized existing literature by conducting a network meta-analysis to determine the most effective first-line ICI combination regimen to guide clinical treatment decisions. Methods We systematically searched the PubMed, Embase, Web of Science, and Cochrane Library databases for Phase III randomised controlled trials published up to 1 August 2024. Eligible studies underscored on patients with driver gene-negative NSCLC with liver metastases and reported progression-free survival (PFS), overall survival (OS), and treatment-related adverse events. Bayesian network meta-analysis was conducted using R (version 4.4.1) and STATA (version 17), with the results reported as hazard ratios (HRs) and 95% confidence intervals (CIs). Results Fourteen studies including 1,291 patients and 11 ICIs combination regimens were included. Pembrolizumab plus chemotherapy remarkably improved OS (HR, 0.64; 95% CI, 0.41–0.98). For PFS, tislelizumab plus chemotherapy (HR, 0.44; 95% CI, 0.26–0.74) and pembrolizumab plus chemotherapy (HR, 0.59; 95% CI, 0.39–0.90) were superior to other treatments. PD-1 inhibitors, such as pembrolizumab, combined with chemotherapy have shown greater efficacy than PD-L1 inhibitors, particularly for non-squamous cell carcinoma. High-grade adverse events, including hepatotoxicity, were more frequent in patients with liver metastases. Conclusion ICI-chemotherapy combinations offer a promising first-line treatment for driver gene-negative NSCLC with liver metastases. The pembrolizumab and tislelizumab combination demonstrated improved OS and PFS with distinct efficacy and safety profiles. Enhanced monitoring of liver function is recommended because of the risk of hepatotoxicity. Further studies are needed to confirm these findings and optimise individualised treatment strategies.
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spelling doaj-art-7e1fa2d7d097496baabfcac880abdd442025-08-20T03:47:10ZengBMCBMC Cancer1471-24072025-08-0125111410.1186/s12885-025-14712-wThe efficacy and safety of immune combination therapy in patients with driver gene-negative non-small cell lung cancer with liver metastasis: a systematic review and network meta-analysisWeixing Zhao0Bo Li1Yujia Gu2Xiaoni Jin3Zirui Li4Wanjing Guo5Xinxin Lu6Jun Jiang7Affiliated Hospital of Qinghai UniversityAffiliated Hospital of Qinghai UniversityAffiliated Hospital of Qinghai UniversityAffiliated Hospital of Qinghai UniversityAffiliated Hospital of Qinghai UniversityAffiliated Hospital of Qinghai UniversityAffiliated Hospital of Qinghai UniversityAffiliated Hospital of Qinghai UniversityAbstract Objective This study aimed to systematically evaluate the efficacy and safety of combination therapies with immune checkpoint inhibitors (ICIs) in patients with driver gene-negative non-small cell lung cancer (NSCLC) and liver metastases. These patients typically have poor prognosis and limited responses to immunotherapy. This study synthesized existing literature by conducting a network meta-analysis to determine the most effective first-line ICI combination regimen to guide clinical treatment decisions. Methods We systematically searched the PubMed, Embase, Web of Science, and Cochrane Library databases for Phase III randomised controlled trials published up to 1 August 2024. Eligible studies underscored on patients with driver gene-negative NSCLC with liver metastases and reported progression-free survival (PFS), overall survival (OS), and treatment-related adverse events. Bayesian network meta-analysis was conducted using R (version 4.4.1) and STATA (version 17), with the results reported as hazard ratios (HRs) and 95% confidence intervals (CIs). Results Fourteen studies including 1,291 patients and 11 ICIs combination regimens were included. Pembrolizumab plus chemotherapy remarkably improved OS (HR, 0.64; 95% CI, 0.41–0.98). For PFS, tislelizumab plus chemotherapy (HR, 0.44; 95% CI, 0.26–0.74) and pembrolizumab plus chemotherapy (HR, 0.59; 95% CI, 0.39–0.90) were superior to other treatments. PD-1 inhibitors, such as pembrolizumab, combined with chemotherapy have shown greater efficacy than PD-L1 inhibitors, particularly for non-squamous cell carcinoma. High-grade adverse events, including hepatotoxicity, were more frequent in patients with liver metastases. Conclusion ICI-chemotherapy combinations offer a promising first-line treatment for driver gene-negative NSCLC with liver metastases. The pembrolizumab and tislelizumab combination demonstrated improved OS and PFS with distinct efficacy and safety profiles. Enhanced monitoring of liver function is recommended because of the risk of hepatotoxicity. Further studies are needed to confirm these findings and optimise individualised treatment strategies.https://doi.org/10.1186/s12885-025-14712-wNSCLCImmune checkpoint inhibitorChemotherapyLiver MetastasisFirst-line therapy
spellingShingle Weixing Zhao
Bo Li
Yujia Gu
Xiaoni Jin
Zirui Li
Wanjing Guo
Xinxin Lu
Jun Jiang
The efficacy and safety of immune combination therapy in patients with driver gene-negative non-small cell lung cancer with liver metastasis: a systematic review and network meta-analysis
BMC Cancer
NSCLC
Immune checkpoint inhibitor
Chemotherapy
Liver Metastasis
First-line therapy
title The efficacy and safety of immune combination therapy in patients with driver gene-negative non-small cell lung cancer with liver metastasis: a systematic review and network meta-analysis
title_full The efficacy and safety of immune combination therapy in patients with driver gene-negative non-small cell lung cancer with liver metastasis: a systematic review and network meta-analysis
title_fullStr The efficacy and safety of immune combination therapy in patients with driver gene-negative non-small cell lung cancer with liver metastasis: a systematic review and network meta-analysis
title_full_unstemmed The efficacy and safety of immune combination therapy in patients with driver gene-negative non-small cell lung cancer with liver metastasis: a systematic review and network meta-analysis
title_short The efficacy and safety of immune combination therapy in patients with driver gene-negative non-small cell lung cancer with liver metastasis: a systematic review and network meta-analysis
title_sort efficacy and safety of immune combination therapy in patients with driver gene negative non small cell lung cancer with liver metastasis a systematic review and network meta analysis
topic NSCLC
Immune checkpoint inhibitor
Chemotherapy
Liver Metastasis
First-line therapy
url https://doi.org/10.1186/s12885-025-14712-w
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