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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| 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. |
| format | Article |
| id | doaj-art-1326f9daa45d4bf2b50a24de04c3ce60 |
| institution | DOAJ |
| issn | 0971-5851 0975-2129 |
| language | English |
| publisher | Thieme Medical and Scientific Publishers Pvt. Ltd. |
| record_format | Article |
| 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 |