Comparative long-term outcomes of first-line CDK4/6 inhibitors plus endocrine therapy versus endocrine therapy in patients with HR+/HER2-metastatic or advanced breast cancer: a meta-analysis

IntroductionThis meta-analysis was designed to compare the long-term outcomes of first-line cyclin-dependent kinase 4/6 (CDK4/6) inhibitors plus endocrine therapy (ET) versus ET in patients with HR+/HER2-metastatic or advanced breast cancer (BC).Materials and methodsFour databases (Medline, Embase,...

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Main Authors: Xiaojian Wang, Xinyi Liang, Chenchen Li, Mengtian Qin, Jianyu Wu, Yuechen Qin, Yue Zou, Haijian Zeng, Chunlan Li, Xiaomeng Huang, Haiyun Tao, Jieru Quan, Xiao Wang
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Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Frontiers in Pharmacology
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Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2025.1600892/full
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author Xiaojian Wang
Xinyi Liang
Chenchen Li
Mengtian Qin
Jianyu Wu
Yuechen Qin
Yue Zou
Haijian Zeng
Chunlan Li
Xiaomeng Huang
Haiyun Tao
Jieru Quan
Xiao Wang
author_facet Xiaojian Wang
Xinyi Liang
Chenchen Li
Mengtian Qin
Jianyu Wu
Yuechen Qin
Yue Zou
Haijian Zeng
Chunlan Li
Xiaomeng Huang
Haiyun Tao
Jieru Quan
Xiao Wang
author_sort Xiaojian Wang
collection DOAJ
description IntroductionThis meta-analysis was designed to compare the long-term outcomes of first-line cyclin-dependent kinase 4/6 (CDK4/6) inhibitors plus endocrine therapy (ET) versus ET in patients with HR+/HER2-metastatic or advanced breast cancer (BC).Materials and methodsFour databases (Medline, Embase, Web of Science, and CENTRAL) were searched for literature comparing First-line CDK4/6 inhibitors plus ET to ET in patients with HR+/HER2-metastatic or advanced breast cancer. The search was conducted from the database’s establishment to April 3, 2025. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and severe treatment-related adverse events (SAEs) were subjected to meta-analyses.ResultsTwelve Randomized controlled trials (RCTs) were included in the meta-analysis. The meta-analysis included a group of 4,957 patients diagnosed with HR+/HER2-metastatic or advanced breast cancer. Within this cohort, 2,877 patients were administered First-line CDK4/6 inhibitors together with ET, while 2080 patients received first-line ET alone. Compared with ET, First-line CDK4/6 inhibitors plus ET yielded superior ORR (RR = 1.39, 95% CI, 1.28 to 1.51, P < 0.01), DCR (RR = 1.09, 95% CI, 1.05 to 1.14, P < 0.01), PFS (HR: 0.57, 95%CI 0.53 to 0.62, P < 0.01) and OS (HR: 0.81, 95%CI 0.73 to 0.89, P < 0.01). Reconstruction of Kaplan-Meier curves for OS and PFS using the IPDformKM program provided a clear and comprehensible representation of oncological outcomes. First-line CDK4/6 inhibitors plus ET was more effective than ET in terms of PFS (median survival time: 27.0 months versus 14.4 months, HR: 0.55, 95%CI 0.51 to 0.59, P < 0.01) and OS (median survival time: 59.6 months versus 50.0 months, HR: 0.79, 95%CI 0.72 to 0.87, P < 0.01). With regards to safety, First-line CDK4/6 inhibitors plus ET exhibited a greater likelihood of encountering SAEs (RR = 1.54, 95% CI: 1.30 to 1.82, P < 0.01) in comparison to ET.ConclusionThe present meta-analysis reported comparative long-term outcomes of CDK4/6 inhibitors plus ET versus ET as first-line therapy for HR+/HER2-metastatic or advanced breast cancer. Compared with ET alone, CDK4/6 inhibitors plus ET as first-line therapy provided improved ORR, DCR, PFS, and OS. Furthermore, the heightened efficacy of CDK4/6 inhibitors plus ET was accompanied by a rise in SAEs.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/view/CRD42024590572, Identifier CRD42024590572.
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spelling doaj-art-275d9d1e8c75498abf985a69ef09e2ab2025-08-20T02:48:17ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-07-011610.3389/fphar.2025.16008921600892Comparative long-term outcomes of first-line CDK4/6 inhibitors plus endocrine therapy versus endocrine therapy in patients with HR+/HER2-metastatic or advanced breast cancer: a meta-analysisXiaojian Wang0Xinyi Liang1Chenchen Li2Mengtian Qin3Jianyu Wu4Yuechen Qin5Yue Zou6Haijian Zeng7Chunlan Li8Xiaomeng Huang9Haiyun Tao10Jieru Quan11Xiao Wang12The First Affiliated Hospital of Guangxi University of Science and Technology, Guangxi University of Science and Technology, Liuzhou, Guangxi, ChinaThe First Affiliated Hospital of Guangxi University of Science and Technology, Guangxi University of Science and Technology, Liuzhou, Guangxi, ChinaDepartment of Medical Oncology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, ChinaThe First Affiliated Hospital of Guangxi University of Science and Technology, Guangxi University of Science and Technology, Liuzhou, Guangxi, ChinaThe First Affiliated Hospital of Guangxi University of Science and Technology, Guangxi University of Science and Technology, Liuzhou, Guangxi, ChinaThe First Affiliated Hospital of Guangxi University of Science and Technology, Guangxi University of Science and Technology, Liuzhou, Guangxi, ChinaThe First Affiliated Hospital of Guangxi University of Science and Technology, Guangxi University of Science and Technology, Liuzhou, Guangxi, ChinaThe First Affiliated Hospital of Guangxi University of Science and Technology, Guangxi University of Science and Technology, Liuzhou, Guangxi, ChinaThe First Affiliated Hospital of Guangxi University of Science and Technology, Guangxi University of Science and Technology, Liuzhou, Guangxi, ChinaThe First Affiliated Hospital of Guangxi University of Science and Technology, Guangxi University of Science and Technology, Liuzhou, Guangxi, ChinaThe First Affiliated Hospital of Guangxi University of Science and Technology, Guangxi University of Science and Technology, Liuzhou, Guangxi, ChinaSchool of Economics and Management, Guangxi University of Science and Technology, Liuzhou, Guangxi, ChinaThe First Affiliated Hospital of Guangxi University of Science and Technology, Guangxi University of Science and Technology, Liuzhou, Guangxi, ChinaIntroductionThis meta-analysis was designed to compare the long-term outcomes of first-line cyclin-dependent kinase 4/6 (CDK4/6) inhibitors plus endocrine therapy (ET) versus ET in patients with HR+/HER2-metastatic or advanced breast cancer (BC).Materials and methodsFour databases (Medline, Embase, Web of Science, and CENTRAL) were searched for literature comparing First-line CDK4/6 inhibitors plus ET to ET in patients with HR+/HER2-metastatic or advanced breast cancer. The search was conducted from the database’s establishment to April 3, 2025. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and severe treatment-related adverse events (SAEs) were subjected to meta-analyses.ResultsTwelve Randomized controlled trials (RCTs) were included in the meta-analysis. The meta-analysis included a group of 4,957 patients diagnosed with HR+/HER2-metastatic or advanced breast cancer. Within this cohort, 2,877 patients were administered First-line CDK4/6 inhibitors together with ET, while 2080 patients received first-line ET alone. Compared with ET, First-line CDK4/6 inhibitors plus ET yielded superior ORR (RR = 1.39, 95% CI, 1.28 to 1.51, P < 0.01), DCR (RR = 1.09, 95% CI, 1.05 to 1.14, P < 0.01), PFS (HR: 0.57, 95%CI 0.53 to 0.62, P < 0.01) and OS (HR: 0.81, 95%CI 0.73 to 0.89, P < 0.01). Reconstruction of Kaplan-Meier curves for OS and PFS using the IPDformKM program provided a clear and comprehensible representation of oncological outcomes. First-line CDK4/6 inhibitors plus ET was more effective than ET in terms of PFS (median survival time: 27.0 months versus 14.4 months, HR: 0.55, 95%CI 0.51 to 0.59, P < 0.01) and OS (median survival time: 59.6 months versus 50.0 months, HR: 0.79, 95%CI 0.72 to 0.87, P < 0.01). With regards to safety, First-line CDK4/6 inhibitors plus ET exhibited a greater likelihood of encountering SAEs (RR = 1.54, 95% CI: 1.30 to 1.82, P < 0.01) in comparison to ET.ConclusionThe present meta-analysis reported comparative long-term outcomes of CDK4/6 inhibitors plus ET versus ET as first-line therapy for HR+/HER2-metastatic or advanced breast cancer. Compared with ET alone, CDK4/6 inhibitors plus ET as first-line therapy provided improved ORR, DCR, PFS, and OS. Furthermore, the heightened efficacy of CDK4/6 inhibitors plus ET was accompanied by a rise in SAEs.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/view/CRD42024590572, Identifier CRD42024590572.https://www.frontiersin.org/articles/10.3389/fphar.2025.1600892/fullbreast cancermetastaticendocrine therapyCDK4/6 inhibitorsprogression-free survivaloverall survival
spellingShingle Xiaojian Wang
Xinyi Liang
Chenchen Li
Mengtian Qin
Jianyu Wu
Yuechen Qin
Yue Zou
Haijian Zeng
Chunlan Li
Xiaomeng Huang
Haiyun Tao
Jieru Quan
Xiao Wang
Comparative long-term outcomes of first-line CDK4/6 inhibitors plus endocrine therapy versus endocrine therapy in patients with HR+/HER2-metastatic or advanced breast cancer: a meta-analysis
Frontiers in Pharmacology
breast cancer
metastatic
endocrine therapy
CDK4/6 inhibitors
progression-free survival
overall survival
title Comparative long-term outcomes of first-line CDK4/6 inhibitors plus endocrine therapy versus endocrine therapy in patients with HR+/HER2-metastatic or advanced breast cancer: a meta-analysis
title_full Comparative long-term outcomes of first-line CDK4/6 inhibitors plus endocrine therapy versus endocrine therapy in patients with HR+/HER2-metastatic or advanced breast cancer: a meta-analysis
title_fullStr Comparative long-term outcomes of first-line CDK4/6 inhibitors plus endocrine therapy versus endocrine therapy in patients with HR+/HER2-metastatic or advanced breast cancer: a meta-analysis
title_full_unstemmed Comparative long-term outcomes of first-line CDK4/6 inhibitors plus endocrine therapy versus endocrine therapy in patients with HR+/HER2-metastatic or advanced breast cancer: a meta-analysis
title_short Comparative long-term outcomes of first-line CDK4/6 inhibitors plus endocrine therapy versus endocrine therapy in patients with HR+/HER2-metastatic or advanced breast cancer: a meta-analysis
title_sort comparative long term outcomes of first line cdk4 6 inhibitors plus endocrine therapy versus endocrine therapy in patients with hr her2 metastatic or advanced breast cancer a meta analysis
topic breast cancer
metastatic
endocrine therapy
CDK4/6 inhibitors
progression-free survival
overall survival
url https://www.frontiersin.org/articles/10.3389/fphar.2025.1600892/full
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