Real-world effectiveness of CDK4/6i in first-line treatment of HR+/HER2− advanced/metastatic breast cancer: updated systematic review

AimSince 2021, additional real-world evidence (RWE) has emerged on the effectiveness of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) as first-line treatment of HR-positive/HER2-negative (HR+/HER2−) advanced/metastatic breast cancer (A/MBC), necessitating this updated review.MethodsMEDLINE®, Emba...

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Main Authors: Nadia Harbeck, Adam Brufsky, Chloe Grace Rose, Beata Korytowsky, Connie Chen, Krista Tantakoun, Endri Jazexhi, Do Hoang Vien Nguyen, Meaghan Bartlett, Imtiaz A. Samjoo, Timothy Pluard
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-03-01
Series:Frontiers in Oncology
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Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2025.1530391/full
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author Nadia Harbeck
Adam Brufsky
Chloe Grace Rose
Beata Korytowsky
Connie Chen
Krista Tantakoun
Endri Jazexhi
Do Hoang Vien Nguyen
Meaghan Bartlett
Imtiaz A. Samjoo
Timothy Pluard
author_facet Nadia Harbeck
Adam Brufsky
Chloe Grace Rose
Beata Korytowsky
Connie Chen
Krista Tantakoun
Endri Jazexhi
Do Hoang Vien Nguyen
Meaghan Bartlett
Imtiaz A. Samjoo
Timothy Pluard
author_sort Nadia Harbeck
collection DOAJ
description AimSince 2021, additional real-world evidence (RWE) has emerged on the effectiveness of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) as first-line treatment of HR-positive/HER2-negative (HR+/HER2−) advanced/metastatic breast cancer (A/MBC), necessitating this updated review.MethodsMEDLINE®, Embase®, and Cochrane Databases (07/06/2019–01/09/2024), and key congresses (2020–2024) were searched. Studies reporting first-line CDK4/6i use, over 100 participants, and progression-free survival (PFS) and/or overall survival (OS) data were included.ResultsThis update included 82 unique studies, 42.7% for palbociclib, 7.3% for ribociclib, and 3.7% for abemaciclib; 46.3% assessed multiple CDK4/6i. In studies including multiple CDK4/6is, median PFS was 23.4–31.0 months for palbociclib, 19.8–44.0 for ribociclib, and 14.0–39.5 for abemaciclib. When reached, median OS was 38.0–58.0 months, 40.4–52.0 months, and 34.4 months, respectively. These real-world PFS and OS results were within the range of single-arm and CDK4/6i versus endocrine therapy (ET) studies, where CDK4/6i demonstrated greater benefits than ET alone.ConclusionFirst-line CDK4/6i RWE demonstrates significant clinical benefits in HR+/HER2− A/MBC. These data are important to guide clinical decision-making, as they include patients who are not adequately represented in clinical trials. Studies with longer follow-up are needed to assess long-term benefits of all three CDK4/6i therapies in HR+/HER2− A/MBC.
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spelling doaj-art-13d5909989ff4263bab059daf2fc8c172025-08-20T01:57:32ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-03-011510.3389/fonc.2025.15303911530391Real-world effectiveness of CDK4/6i in first-line treatment of HR+/HER2− advanced/metastatic breast cancer: updated systematic reviewNadia Harbeck0Adam Brufsky1Chloe Grace Rose2Beata Korytowsky3Connie Chen4Krista Tantakoun5Endri Jazexhi6Do Hoang Vien Nguyen7Meaghan Bartlett8Imtiaz A. Samjoo9Timothy Pluard10Breast Center, Department of Gynecology and Obstetrics and Comprehensive Cancer Center Munich, LMU University Hospital, Munich, GermanyUPMC Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, PA, United StatesPfizer, Inc., New York, NY, United StatesPfizer, Inc., New York, NY, United StatesPfizer, Inc., New York, NY, United StatesValue & Evidence, EVERSANATM, Burlington, ON, CanadaValue & Evidence, EVERSANATM, Burlington, ON, CanadaValue & Evidence, EVERSANATM, Burlington, ON, CanadaValue & Evidence, EVERSANATM, Burlington, ON, CanadaValue & Evidence, EVERSANATM, Burlington, ON, CanadaHematology and Medical Oncology, St. Luke's Cancer Institute, Kansas City, MO, United StatesAimSince 2021, additional real-world evidence (RWE) has emerged on the effectiveness of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) as first-line treatment of HR-positive/HER2-negative (HR+/HER2−) advanced/metastatic breast cancer (A/MBC), necessitating this updated review.MethodsMEDLINE®, Embase®, and Cochrane Databases (07/06/2019–01/09/2024), and key congresses (2020–2024) were searched. Studies reporting first-line CDK4/6i use, over 100 participants, and progression-free survival (PFS) and/or overall survival (OS) data were included.ResultsThis update included 82 unique studies, 42.7% for palbociclib, 7.3% for ribociclib, and 3.7% for abemaciclib; 46.3% assessed multiple CDK4/6i. In studies including multiple CDK4/6is, median PFS was 23.4–31.0 months for palbociclib, 19.8–44.0 for ribociclib, and 14.0–39.5 for abemaciclib. When reached, median OS was 38.0–58.0 months, 40.4–52.0 months, and 34.4 months, respectively. These real-world PFS and OS results were within the range of single-arm and CDK4/6i versus endocrine therapy (ET) studies, where CDK4/6i demonstrated greater benefits than ET alone.ConclusionFirst-line CDK4/6i RWE demonstrates significant clinical benefits in HR+/HER2− A/MBC. These data are important to guide clinical decision-making, as they include patients who are not adequately represented in clinical trials. Studies with longer follow-up are needed to assess long-term benefits of all three CDK4/6i therapies in HR+/HER2− A/MBC.https://www.frontiersin.org/articles/10.3389/fonc.2025.1530391/fullCDK4/6 inhibitorsquality assessmentbreastmetastasisreal-world evidencesystematic literature review
spellingShingle Nadia Harbeck
Adam Brufsky
Chloe Grace Rose
Beata Korytowsky
Connie Chen
Krista Tantakoun
Endri Jazexhi
Do Hoang Vien Nguyen
Meaghan Bartlett
Imtiaz A. Samjoo
Timothy Pluard
Real-world effectiveness of CDK4/6i in first-line treatment of HR+/HER2− advanced/metastatic breast cancer: updated systematic review
Frontiers in Oncology
CDK4/6 inhibitors
quality assessment
breast
metastasis
real-world evidence
systematic literature review
title Real-world effectiveness of CDK4/6i in first-line treatment of HR+/HER2− advanced/metastatic breast cancer: updated systematic review
title_full Real-world effectiveness of CDK4/6i in first-line treatment of HR+/HER2− advanced/metastatic breast cancer: updated systematic review
title_fullStr Real-world effectiveness of CDK4/6i in first-line treatment of HR+/HER2− advanced/metastatic breast cancer: updated systematic review
title_full_unstemmed Real-world effectiveness of CDK4/6i in first-line treatment of HR+/HER2− advanced/metastatic breast cancer: updated systematic review
title_short Real-world effectiveness of CDK4/6i in first-line treatment of HR+/HER2− advanced/metastatic breast cancer: updated systematic review
title_sort real world effectiveness of cdk4 6i in first line treatment of hr her2 advanced metastatic breast cancer updated systematic review
topic CDK4/6 inhibitors
quality assessment
breast
metastasis
real-world evidence
systematic literature review
url https://www.frontiersin.org/articles/10.3389/fonc.2025.1530391/full
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