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Tyrosine kinase inhibitors in HER2‐positive breast cancer brain metastases: A systematic review and meta‐analysis

BACKGROUND: Small tyrosine kinase inhibitors (TKIs) show activity against breast cancer brain metastases (BCBM) of the human epidermal growth factor receptor 2 (HER2)‐positive subtype. This meta‐analysis aimed to objectively explore the efficacy and safety of TKIs. METHODS: Electronic databases were...

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Autores principales: Yu, Yushuai, Huang, Kaiyan, Lin, Yuxiang, Zhang, Jie, Song, Chuangui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10417165/
https://www.ncbi.nlm.nih.gov/pubmed/37255389
http://dx.doi.org/10.1002/cam4.6180
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author Yu, Yushuai
Huang, Kaiyan
Lin, Yuxiang
Zhang, Jie
Song, Chuangui
author_facet Yu, Yushuai
Huang, Kaiyan
Lin, Yuxiang
Zhang, Jie
Song, Chuangui
author_sort Yu, Yushuai
collection PubMed
description BACKGROUND: Small tyrosine kinase inhibitors (TKIs) show activity against breast cancer brain metastases (BCBM) of the human epidermal growth factor receptor 2 (HER2)‐positive subtype. This meta‐analysis aimed to objectively explore the efficacy and safety of TKIs. METHODS: Electronic databases were searched for relevant clinical trials. We conducted a pairwise meta‐analysis, pooled analysis, and estimated summary survival curves to compare survival outcomes following TKIs therapy for BCBM patients using Stata version 16.0 or R x64 4.0.5. RESULTS: Thirteen clinical trials involving 987 HER2‐positive BCBM patients were analyzed. A trend of longer progression‐free survival (PFS) was observed in the TKI‐containing arm compared to the non‐TKI‐containing arm (hazard ratio = 0.64, 95% confidence interval [CI]: 0.35–1.15, p = 0.132), although the difference is not statistically significant. Summary survival curves reported the summary median PFS and overall survival were 7.9 months and 12.3 months. Subgroup analysis revealed that TKIs combined with capecitabine (TKI + Cap) regimens resulted in improved survival outcomes. Tucatinib may be more effective in BCBM patients. The main grade 3–5 adverse events (AEs) were diarrhea (22%, 95% CI: 14%–32%), neutropenia (11%, 95% CI: 5%–18%), hepatic toxicity (7%, 95% CI: 1%–16%), and sensory neuropathy (6%, 95% CI: 2%–12%). CONCLUSION: TKIs therapy improved the survival outcomes of HER2‐positive BCBM patients, especially when combined with capecitabine and tolerable AEs. We also identified the clinical value of tucatinib, which appears to be the most favorable TKI drug for BCBM patients.
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spelling pubmed-104171652023-08-12 Tyrosine kinase inhibitors in HER2‐positive breast cancer brain metastases: A systematic review and meta‐analysis Yu, Yushuai Huang, Kaiyan Lin, Yuxiang Zhang, Jie Song, Chuangui Cancer Med RESEARCH ARTICLES BACKGROUND: Small tyrosine kinase inhibitors (TKIs) show activity against breast cancer brain metastases (BCBM) of the human epidermal growth factor receptor 2 (HER2)‐positive subtype. This meta‐analysis aimed to objectively explore the efficacy and safety of TKIs. METHODS: Electronic databases were searched for relevant clinical trials. We conducted a pairwise meta‐analysis, pooled analysis, and estimated summary survival curves to compare survival outcomes following TKIs therapy for BCBM patients using Stata version 16.0 or R x64 4.0.5. RESULTS: Thirteen clinical trials involving 987 HER2‐positive BCBM patients were analyzed. A trend of longer progression‐free survival (PFS) was observed in the TKI‐containing arm compared to the non‐TKI‐containing arm (hazard ratio = 0.64, 95% confidence interval [CI]: 0.35–1.15, p = 0.132), although the difference is not statistically significant. Summary survival curves reported the summary median PFS and overall survival were 7.9 months and 12.3 months. Subgroup analysis revealed that TKIs combined with capecitabine (TKI + Cap) regimens resulted in improved survival outcomes. Tucatinib may be more effective in BCBM patients. The main grade 3–5 adverse events (AEs) were diarrhea (22%, 95% CI: 14%–32%), neutropenia (11%, 95% CI: 5%–18%), hepatic toxicity (7%, 95% CI: 1%–16%), and sensory neuropathy (6%, 95% CI: 2%–12%). CONCLUSION: TKIs therapy improved the survival outcomes of HER2‐positive BCBM patients, especially when combined with capecitabine and tolerable AEs. We also identified the clinical value of tucatinib, which appears to be the most favorable TKI drug for BCBM patients. John Wiley and Sons Inc. 2023-05-31 /pmc/articles/PMC10417165/ /pubmed/37255389 http://dx.doi.org/10.1002/cam4.6180 Text en © 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle RESEARCH ARTICLES
Yu, Yushuai
Huang, Kaiyan
Lin, Yuxiang
Zhang, Jie
Song, Chuangui
Tyrosine kinase inhibitors in HER2‐positive breast cancer brain metastases: A systematic review and meta‐analysis
title Tyrosine kinase inhibitors in HER2‐positive breast cancer brain metastases: A systematic review and meta‐analysis
title_full Tyrosine kinase inhibitors in HER2‐positive breast cancer brain metastases: A systematic review and meta‐analysis
title_fullStr Tyrosine kinase inhibitors in HER2‐positive breast cancer brain metastases: A systematic review and meta‐analysis
title_full_unstemmed Tyrosine kinase inhibitors in HER2‐positive breast cancer brain metastases: A systematic review and meta‐analysis
title_short Tyrosine kinase inhibitors in HER2‐positive breast cancer brain metastases: A systematic review and meta‐analysis
title_sort tyrosine kinase inhibitors in her2‐positive breast cancer brain metastases: a systematic review and meta‐analysis
topic RESEARCH ARTICLES
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10417165/
https://www.ncbi.nlm.nih.gov/pubmed/37255389
http://dx.doi.org/10.1002/cam4.6180
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