Optimizing Post-CDK4/6i Strategies In HR +/HER2− Advanced Breast Cancer: A Contemporary Evidence-Based Framework

The advent of CDK4/6 inhibitors has transformed the frontline management of HR +/HER2− metastatic breast cancer. However, resistance to these agents is inevitable, leading to a growing need for evidence-based post-progression strategies. This review synthesizes data from major trials—SONIA, PALMIRA,...

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Main Authors: Teena Rajan, Amol Akhade
Format: Article
Language:English
Published: Thieme Medical and Scientific Publishers Pvt. Ltd.
Series:Indian Journal of Medical and Paediatric Oncology
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Online Access:http://www.thieme-connect.de/DOI/DOI?10.1055/s-0045-1810005
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author Teena Rajan
Amol Akhade
author_facet Teena Rajan
Amol Akhade
author_sort Teena Rajan
collection DOAJ
description The advent of CDK4/6 inhibitors has transformed the frontline management of HR +/HER2− metastatic breast cancer. However, resistance to these agents is inevitable, leading to a growing need for evidence-based post-progression strategies. This review synthesizes data from major trials—SONIA, PALMIRA, MAINTAIN, postMONARCH, and EMBER-3—exploring both rechallenge and class-switching strategies. We evaluate the clinical impact of switching versus continuing CDK4/6 inhibitors, mechanisms of resistance, and emerging agents such as oral SERDs (selective estrogen receptor degraders) and PROTACs. The evidence suggests limited benefit for same-agent rechallenge and supports the use of novel combinations in biomarker-selected populations. Personalized sequencing guided by molecular profiling may define the next frontier in HR +/HER2− metastatic breast cancer management.
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series Indian Journal of Medical and Paediatric Oncology
spelling doaj-art-1326f9daa45d4bf2b50a24de04c3ce602025-08-20T02:40:27ZengThieme Medical and Scientific Publishers Pvt. Ltd.Indian Journal of Medical and Paediatric Oncology0971-58510975-212910.1055/s-0045-1810005Optimizing Post-CDK4/6i Strategies In HR +/HER2− Advanced Breast Cancer: A Contemporary Evidence-Based FrameworkTeena Rajan0Amol Akhade1Department of Medical Oncology, N. Sreedharan Memorial Institute of Medical Sciences, Kollam, Kerala, IndiaDepartment of Medical Oncology, Nair Hospital, Mumbai, Maharashtra, IndiaThe advent of CDK4/6 inhibitors has transformed the frontline management of HR +/HER2− metastatic breast cancer. However, resistance to these agents is inevitable, leading to a growing need for evidence-based post-progression strategies. This review synthesizes data from major trials—SONIA, PALMIRA, MAINTAIN, postMONARCH, and EMBER-3—exploring both rechallenge and class-switching strategies. We evaluate the clinical impact of switching versus continuing CDK4/6 inhibitors, mechanisms of resistance, and emerging agents such as oral SERDs (selective estrogen receptor degraders) and PROTACs. The evidence suggests limited benefit for same-agent rechallenge and supports the use of novel combinations in biomarker-selected populations. Personalized sequencing guided by molecular profiling may define the next frontier in HR +/HER2− metastatic breast cancer management.http://www.thieme-connect.de/DOI/DOI?10.1055/s-0045-1810005HR+ breast cancerCDK4/6 inhibitorsSERDsendocrine resistanceimlunestrantbiomarker-driven treatment
spellingShingle Teena Rajan
Amol Akhade
Optimizing Post-CDK4/6i Strategies In HR +/HER2− Advanced Breast Cancer: A Contemporary Evidence-Based Framework
Indian Journal of Medical and Paediatric Oncology
HR+ breast cancer
CDK4/6 inhibitors
SERDs
endocrine resistance
imlunestrant
biomarker-driven treatment
title Optimizing Post-CDK4/6i Strategies In HR +/HER2− Advanced Breast Cancer: A Contemporary Evidence-Based Framework
title_full Optimizing Post-CDK4/6i Strategies In HR +/HER2− Advanced Breast Cancer: A Contemporary Evidence-Based Framework
title_fullStr Optimizing Post-CDK4/6i Strategies In HR +/HER2− Advanced Breast Cancer: A Contemporary Evidence-Based Framework
title_full_unstemmed Optimizing Post-CDK4/6i Strategies In HR +/HER2− Advanced Breast Cancer: A Contemporary Evidence-Based Framework
title_short Optimizing Post-CDK4/6i Strategies In HR +/HER2− Advanced Breast Cancer: A Contemporary Evidence-Based Framework
title_sort optimizing post cdk4 6i strategies in hr her2 advanced breast cancer a contemporary evidence based framework
topic HR+ breast cancer
CDK4/6 inhibitors
SERDs
endocrine resistance
imlunestrant
biomarker-driven treatment
url http://www.thieme-connect.de/DOI/DOI?10.1055/s-0045-1810005
work_keys_str_mv AT teenarajan optimizingpostcdk46istrategiesinhrher2advancedbreastcanceracontemporaryevidencebasedframework
AT amolakhade optimizingpostcdk46istrategiesinhrher2advancedbreastcanceracontemporaryevidencebasedframework