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Combination cyclin-dependent kinase 4/6 inhibitors and endocrine therapy versus endocrine monotherapy for hormonal receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: A systematic review and meta-analysis

PURPOSE: This meta-analysis aimed to assess the efficacy and safety of cyclin-dependent kinase (CDK) 4/6 inhibitors plus endocrine therapy (ET) in hormonal receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC). METHODS: We searched PubMed, Em...

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Autores principales: Zheng, Jiani, Wu, Jingxun, Wang, Chunyue, Zhuang, Shiwen, Chen, Jianbo, Ye, Feng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7272037/
https://www.ncbi.nlm.nih.gov/pubmed/32497134
http://dx.doi.org/10.1371/journal.pone.0233571
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author Zheng, Jiani
Wu, Jingxun
Wang, Chunyue
Zhuang, Shiwen
Chen, Jianbo
Ye, Feng
author_facet Zheng, Jiani
Wu, Jingxun
Wang, Chunyue
Zhuang, Shiwen
Chen, Jianbo
Ye, Feng
author_sort Zheng, Jiani
collection PubMed
description PURPOSE: This meta-analysis aimed to assess the efficacy and safety of cyclin-dependent kinase (CDK) 4/6 inhibitors plus endocrine therapy (ET) in hormonal receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC). METHODS: We searched PubMed, Embase, Cochrane, ClinicalTrials.gov., ASCO, ESMO and AACR databases from inception to October 10, 2019 for randomized controlled trials (RCTs) that compared CDK 4/6 inhibitors plus ET to single-agent ET with no treatment-line restriction. The main outcomes analyzed were progression-free survival (PFS), overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR), and adverse events (AEs). RESULTS: Of 938 identified studies, 9 RCTs with 5043 women were eligible and included. Compared with ET alone, CDK 4/6 inhibitors and ET combination improved in PFS (hazard ratio (HR) 0.54, 95% confidence interval (CI) 0.50–0.59, p< 0.00001) and OS (HR 0.77, 95% CI 0.69–0.85, p< 0.00001), regardless of ET strategies (HR 0.54, 95% CI 0.50–0.59 in PFS; HR 0.77, 95% CI 0.69–0.85 in OS), treatment line of advanced disease (HR 0.52, 95% CI 0.46–0.59 in PFS; HR 0.75, 95% CI 0.66–0.85 in OS) and menopausal status (HR 0.54, 95% CI 0.50–0.58 in PFS; HR 0.76, 95% CI 0.68–0.84 in OS). Higher risk of grade 3/4 AEs (RR 2.66, 95% CI 2.44–2.90, p < 0.00001) were observed in the combination group than in the ET group. CONCLUSIONS: Combination therapy with CDK 4/6 inhibitors and ET prolongs survival in HR+/ HER2- ABC. This combination is a better therapeutic strategy than endocrine monotherapy in HR+/HER2- ABC, regardless of treatment line, menopausal status and other individual characteristics.
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spelling pubmed-72720372020-06-12 Combination cyclin-dependent kinase 4/6 inhibitors and endocrine therapy versus endocrine monotherapy for hormonal receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: A systematic review and meta-analysis Zheng, Jiani Wu, Jingxun Wang, Chunyue Zhuang, Shiwen Chen, Jianbo Ye, Feng PLoS One Research Article PURPOSE: This meta-analysis aimed to assess the efficacy and safety of cyclin-dependent kinase (CDK) 4/6 inhibitors plus endocrine therapy (ET) in hormonal receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC). METHODS: We searched PubMed, Embase, Cochrane, ClinicalTrials.gov., ASCO, ESMO and AACR databases from inception to October 10, 2019 for randomized controlled trials (RCTs) that compared CDK 4/6 inhibitors plus ET to single-agent ET with no treatment-line restriction. The main outcomes analyzed were progression-free survival (PFS), overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR), and adverse events (AEs). RESULTS: Of 938 identified studies, 9 RCTs with 5043 women were eligible and included. Compared with ET alone, CDK 4/6 inhibitors and ET combination improved in PFS (hazard ratio (HR) 0.54, 95% confidence interval (CI) 0.50–0.59, p< 0.00001) and OS (HR 0.77, 95% CI 0.69–0.85, p< 0.00001), regardless of ET strategies (HR 0.54, 95% CI 0.50–0.59 in PFS; HR 0.77, 95% CI 0.69–0.85 in OS), treatment line of advanced disease (HR 0.52, 95% CI 0.46–0.59 in PFS; HR 0.75, 95% CI 0.66–0.85 in OS) and menopausal status (HR 0.54, 95% CI 0.50–0.58 in PFS; HR 0.76, 95% CI 0.68–0.84 in OS). Higher risk of grade 3/4 AEs (RR 2.66, 95% CI 2.44–2.90, p < 0.00001) were observed in the combination group than in the ET group. CONCLUSIONS: Combination therapy with CDK 4/6 inhibitors and ET prolongs survival in HR+/ HER2- ABC. This combination is a better therapeutic strategy than endocrine monotherapy in HR+/HER2- ABC, regardless of treatment line, menopausal status and other individual characteristics. Public Library of Science 2020-06-04 /pmc/articles/PMC7272037/ /pubmed/32497134 http://dx.doi.org/10.1371/journal.pone.0233571 Text en © 2020 Zheng et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Zheng, Jiani
Wu, Jingxun
Wang, Chunyue
Zhuang, Shiwen
Chen, Jianbo
Ye, Feng
Combination cyclin-dependent kinase 4/6 inhibitors and endocrine therapy versus endocrine monotherapy for hormonal receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: A systematic review and meta-analysis
title Combination cyclin-dependent kinase 4/6 inhibitors and endocrine therapy versus endocrine monotherapy for hormonal receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: A systematic review and meta-analysis
title_full Combination cyclin-dependent kinase 4/6 inhibitors and endocrine therapy versus endocrine monotherapy for hormonal receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: A systematic review and meta-analysis
title_fullStr Combination cyclin-dependent kinase 4/6 inhibitors and endocrine therapy versus endocrine monotherapy for hormonal receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: A systematic review and meta-analysis
title_full_unstemmed Combination cyclin-dependent kinase 4/6 inhibitors and endocrine therapy versus endocrine monotherapy for hormonal receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: A systematic review and meta-analysis
title_short Combination cyclin-dependent kinase 4/6 inhibitors and endocrine therapy versus endocrine monotherapy for hormonal receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: A systematic review and meta-analysis
title_sort combination cyclin-dependent kinase 4/6 inhibitors and endocrine therapy versus endocrine monotherapy for hormonal receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: a systematic review and meta-analysis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7272037/
https://www.ncbi.nlm.nih.gov/pubmed/32497134
http://dx.doi.org/10.1371/journal.pone.0233571
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