The efficacy and safety of intrathecal pemetrexed for leptomeningeal metastasis from non-small cell lung cancer: a single-arm meta-analysis of Chinese patients

ObjectivesThe purpose of this meta-analysis is to evaluate the safety and effectiveness of intrathecal pemetrexed (IP) in patients with non-small cell lung cancer with leptomeningeal metastasis (NSCLC-LM).MethodsA systematic search of PubMed, the Cochrane library, Embase, and ClinicalTrials.gov data...

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Main Authors: Yushi Zhao, Xueqin Gao, Yong Han
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-06-01
Series:Frontiers in Oncology
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Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2025.1543416/full
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author Yushi Zhao
Xueqin Gao
Yong Han
author_facet Yushi Zhao
Xueqin Gao
Yong Han
author_sort Yushi Zhao
collection DOAJ
description ObjectivesThe purpose of this meta-analysis is to evaluate the safety and effectiveness of intrathecal pemetrexed (IP) in patients with non-small cell lung cancer with leptomeningeal metastasis (NSCLC-LM).MethodsA systematic search of PubMed, the Cochrane library, Embase, and ClinicalTrials.gov databases was executed until December 11, 2024. The quality of the selected studies was evaluated using the Risk Of Bias In Non-randomized Studies Of Interventions (ROBINS-I) tool. Data extracted encompassed disease control rate (DCR), objective response rate (ORR), median overall survival (mOS), and adverse events (AEs). A random-effects model was used in the meta-analysis, which was conducted using STATA 15.1 software. Egger’s and Begg’s tests were used to analyze publication bias, and when significant publication bias was detected, the Trim and Fill method was employed to adjust for the bias.ResultsThis meta-analysis included 8 studies involving a total of 306 patients, with a pooled ORR of 57.6% (95% CI: 39.5%-74.7%). Further subgroup analysis revealed that a pemetrexed dosage of 40–50 mg exhibited superior efficacy, with an ORR of 84.5% (95% CI: 70.0%-95.6%), compared to an ORR of 46.6% (95% CI: 29.2%-64.4%) for dosages of 10–30 mg. Additionally, patients with EGFR mutations exhibited an ORR of 56.2% (95% CI: 34.7%-76.6%), while those with other genetic subtypes had an ORR of 44.8% (95% CI: 25.1%-65.1%). The combined DCR was 85.4% (95% CI: 76.5%-92.7). In terms of survival, the pooled data from 6 studies yielded a mOS of 8.12 months (95% CI: 6.07-10.17). Common adverse events associated with pemetrexed included myelosuppression (32.6%), headache (24.8%), abnormal transaminase (11.8%), nausea (7.3%), vomiting (11.7%), radiculitis (8.4%) and leukoencephalopathy (6.4%). Potential publication bias was identified for DCR and grade≥III myelosuppression. Subgroup analyses performed by DCR showed that the bias was related to drug dosage, while the Trim and Fill method for grade ≥III myelosuppression did not reverse the bias. These findings suggest that publication bias had minimal impact and that the results were relatively stable.ConclusionsThis meta-analysis concludes that patients with NSCLC-LM benefit from intrathecal chemotherapy using pemetrexed.
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spelling doaj-art-ca2754dd28ed45b981a87be0d43ed66f2025-08-20T03:51:48ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-06-011510.3389/fonc.2025.15434161543416The efficacy and safety of intrathecal pemetrexed for leptomeningeal metastasis from non-small cell lung cancer: a single-arm meta-analysis of Chinese patientsYushi ZhaoXueqin GaoYong HanObjectivesThe purpose of this meta-analysis is to evaluate the safety and effectiveness of intrathecal pemetrexed (IP) in patients with non-small cell lung cancer with leptomeningeal metastasis (NSCLC-LM).MethodsA systematic search of PubMed, the Cochrane library, Embase, and ClinicalTrials.gov databases was executed until December 11, 2024. The quality of the selected studies was evaluated using the Risk Of Bias In Non-randomized Studies Of Interventions (ROBINS-I) tool. Data extracted encompassed disease control rate (DCR), objective response rate (ORR), median overall survival (mOS), and adverse events (AEs). A random-effects model was used in the meta-analysis, which was conducted using STATA 15.1 software. Egger’s and Begg’s tests were used to analyze publication bias, and when significant publication bias was detected, the Trim and Fill method was employed to adjust for the bias.ResultsThis meta-analysis included 8 studies involving a total of 306 patients, with a pooled ORR of 57.6% (95% CI: 39.5%-74.7%). Further subgroup analysis revealed that a pemetrexed dosage of 40–50 mg exhibited superior efficacy, with an ORR of 84.5% (95% CI: 70.0%-95.6%), compared to an ORR of 46.6% (95% CI: 29.2%-64.4%) for dosages of 10–30 mg. Additionally, patients with EGFR mutations exhibited an ORR of 56.2% (95% CI: 34.7%-76.6%), while those with other genetic subtypes had an ORR of 44.8% (95% CI: 25.1%-65.1%). The combined DCR was 85.4% (95% CI: 76.5%-92.7). In terms of survival, the pooled data from 6 studies yielded a mOS of 8.12 months (95% CI: 6.07-10.17). Common adverse events associated with pemetrexed included myelosuppression (32.6%), headache (24.8%), abnormal transaminase (11.8%), nausea (7.3%), vomiting (11.7%), radiculitis (8.4%) and leukoencephalopathy (6.4%). Potential publication bias was identified for DCR and grade≥III myelosuppression. Subgroup analyses performed by DCR showed that the bias was related to drug dosage, while the Trim and Fill method for grade ≥III myelosuppression did not reverse the bias. These findings suggest that publication bias had minimal impact and that the results were relatively stable.ConclusionsThis meta-analysis concludes that patients with NSCLC-LM benefit from intrathecal chemotherapy using pemetrexed.https://www.frontiersin.org/articles/10.3389/fonc.2025.1543416/fullpemetrexednon-small cell lung cancerleptomeningeal metastasismeta-analysisefficacysafety
spellingShingle Yushi Zhao
Xueqin Gao
Yong Han
The efficacy and safety of intrathecal pemetrexed for leptomeningeal metastasis from non-small cell lung cancer: a single-arm meta-analysis of Chinese patients
Frontiers in Oncology
pemetrexed
non-small cell lung cancer
leptomeningeal metastasis
meta-analysis
efficacy
safety
title The efficacy and safety of intrathecal pemetrexed for leptomeningeal metastasis from non-small cell lung cancer: a single-arm meta-analysis of Chinese patients
title_full The efficacy and safety of intrathecal pemetrexed for leptomeningeal metastasis from non-small cell lung cancer: a single-arm meta-analysis of Chinese patients
title_fullStr The efficacy and safety of intrathecal pemetrexed for leptomeningeal metastasis from non-small cell lung cancer: a single-arm meta-analysis of Chinese patients
title_full_unstemmed The efficacy and safety of intrathecal pemetrexed for leptomeningeal metastasis from non-small cell lung cancer: a single-arm meta-analysis of Chinese patients
title_short The efficacy and safety of intrathecal pemetrexed for leptomeningeal metastasis from non-small cell lung cancer: a single-arm meta-analysis of Chinese patients
title_sort efficacy and safety of intrathecal pemetrexed for leptomeningeal metastasis from non small cell lung cancer a single arm meta analysis of chinese patients
topic pemetrexed
non-small cell lung cancer
leptomeningeal metastasis
meta-analysis
efficacy
safety
url https://www.frontiersin.org/articles/10.3389/fonc.2025.1543416/full
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