Systematic Review and Network Meta-Analysis on Treating Hormone Receptor-Positive Metastatic Breast Cancer After CDK4/6 Inhibitors
Introduction: The optimal treatment of estrogen receptor-positive (ER +) metastatic breast cancer (MBC) after progression on cyclin-dependent 4/6 kinase inhibitors (CDK4/6i) is unknown. Methods: We conducted a systematic review and network meta-analysis (NMA) of phase-II/-III randomized trials of ER...
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MDPI AG
2025-01-01
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| Series: | Current Oncology |
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| Online Access: | https://www.mdpi.com/1718-7729/32/1/53 |
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| author | Neha Pathak Abhenil Mittal Sudhir Kumar Chitrakshi Nagpal Eitan Amir Partha Haldar Bharath B. Gangadharaiah Akash Kumar Ashutosh Mishra Atul Batra |
| author_facet | Neha Pathak Abhenil Mittal Sudhir Kumar Chitrakshi Nagpal Eitan Amir Partha Haldar Bharath B. Gangadharaiah Akash Kumar Ashutosh Mishra Atul Batra |
| author_sort | Neha Pathak |
| collection | DOAJ |
| description | Introduction: The optimal treatment of estrogen receptor-positive (ER +) metastatic breast cancer (MBC) after progression on cyclin-dependent 4/6 kinase inhibitors (CDK4/6i) is unknown. Methods: We conducted a systematic review and network meta-analysis (NMA) of phase-II/-III randomized trials of ER + MBC post CDK4/6i + ET progression. We calculated the hazard ratio (HR) for progression-free survival (PFS) and overall survival (OS) using generic inverse variance and odds ratios (ORs) using the Mantel–Haenszel method for adverse events (AEs) with Review-Manager version-5.4. NMA was executed using WINBUGS (Microsoft Excel). Three molecular subgroups were analyzed: HER2-low, PI3K/AKT/mTOR, and the ESR1 mutation subgroup for selective estrogen receptor degrader (SERD). Results: A total of 14 studies were included. In the HER2-low group, Sacituzumab govitecan and trastuzumab deruxtecan had a similar efficacy (HR, 95% CI): PFS (0.98; 0.63–1.43) and OS (1.08; 0.76–1.55). In PI3K/AKT/mTOR-altered cases, capivasertib was superior to alpelisib PFS (0.77; 0.53–1.12), and OS (0.80; 0.48–1.35). SERDs had worse PFS and OS versus ongoing CDK 4/6i (ribociclib). Conclusion: No therapy emerged as the unequivocal choice in the post-CDK 4/6i domain in unselected subgroups. In the HER2-low population, a similar efficacy and different toxicity spectrum was seen. In AKT-altered tumors, capivasertib was less toxic than alpelisib. PROSPERO ID: CRD4202236412. |
| format | Article |
| id | doaj-art-ca9b184d34d84b09bc8e82289f8f4a7e |
| institution | Kabale University |
| issn | 1198-0052 1718-7729 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
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| series | Current Oncology |
| spelling | doaj-art-ca9b184d34d84b09bc8e82289f8f4a7e2025-01-24T13:28:30ZengMDPI AGCurrent Oncology1198-00521718-77292025-01-013215310.3390/curroncol32010053Systematic Review and Network Meta-Analysis on Treating Hormone Receptor-Positive Metastatic Breast Cancer After CDK4/6 InhibitorsNeha Pathak0Abhenil Mittal1Sudhir Kumar2Chitrakshi Nagpal3Eitan Amir4Partha Haldar5Bharath B. Gangadharaiah6Akash Kumar7Ashutosh Mishra8Atul Batra9Division of Medical Oncology & Hematology, Department of Medicine, Princess Margaret Cancer Centre, Toronto, ON M5G 2M9, CanadaHealth Sciences North, Northern Ontario School of Medicine (NOSM U), Sudbury, ON P3E 5J1, CanadaDepartment of Medicine, University of Toronto, Toronto, ON M5S 1A1, CanadaDepartment of Medical Oncology, All India Institute of Medical Sciences, New Delhi 110029, IndiaDivision of Medical Oncology & Hematology, Department of Medicine, Princess Margaret Cancer Centre, Toronto, ON M5G 2M9, CanadaCentre for Community Medicine, All India Institute of Medical Sciences, New Delhi 110029, IndiaDepartment of Medical Oncology, All India Institute of Medical Sciences, New Delhi 110029, IndiaDepartment of Medical Oncology, All India Institute of Medical Sciences, New Delhi 110029, IndiaDepartment of Surgical Oncology, All India Institute of Medical Sciences, New Delhi 110029, IndiaDepartment of Medical Oncology, All India Institute of Medical Sciences, New Delhi 110029, IndiaIntroduction: The optimal treatment of estrogen receptor-positive (ER +) metastatic breast cancer (MBC) after progression on cyclin-dependent 4/6 kinase inhibitors (CDK4/6i) is unknown. Methods: We conducted a systematic review and network meta-analysis (NMA) of phase-II/-III randomized trials of ER + MBC post CDK4/6i + ET progression. We calculated the hazard ratio (HR) for progression-free survival (PFS) and overall survival (OS) using generic inverse variance and odds ratios (ORs) using the Mantel–Haenszel method for adverse events (AEs) with Review-Manager version-5.4. NMA was executed using WINBUGS (Microsoft Excel). Three molecular subgroups were analyzed: HER2-low, PI3K/AKT/mTOR, and the ESR1 mutation subgroup for selective estrogen receptor degrader (SERD). Results: A total of 14 studies were included. In the HER2-low group, Sacituzumab govitecan and trastuzumab deruxtecan had a similar efficacy (HR, 95% CI): PFS (0.98; 0.63–1.43) and OS (1.08; 0.76–1.55). In PI3K/AKT/mTOR-altered cases, capivasertib was superior to alpelisib PFS (0.77; 0.53–1.12), and OS (0.80; 0.48–1.35). SERDs had worse PFS and OS versus ongoing CDK 4/6i (ribociclib). Conclusion: No therapy emerged as the unequivocal choice in the post-CDK 4/6i domain in unselected subgroups. In the HER2-low population, a similar efficacy and different toxicity spectrum was seen. In AKT-altered tumors, capivasertib was less toxic than alpelisib. PROSPERO ID: CRD4202236412.https://www.mdpi.com/1718-7729/32/1/53metastatic breast cancerCDK4/6 inhibitorhormone receptor-positive cancerSERDHER2-low breast cancerAKT inhibitor |
| spellingShingle | Neha Pathak Abhenil Mittal Sudhir Kumar Chitrakshi Nagpal Eitan Amir Partha Haldar Bharath B. Gangadharaiah Akash Kumar Ashutosh Mishra Atul Batra Systematic Review and Network Meta-Analysis on Treating Hormone Receptor-Positive Metastatic Breast Cancer After CDK4/6 Inhibitors Current Oncology metastatic breast cancer CDK4/6 inhibitor hormone receptor-positive cancer SERD HER2-low breast cancer AKT inhibitor |
| title | Systematic Review and Network Meta-Analysis on Treating Hormone Receptor-Positive Metastatic Breast Cancer After CDK4/6 Inhibitors |
| title_full | Systematic Review and Network Meta-Analysis on Treating Hormone Receptor-Positive Metastatic Breast Cancer After CDK4/6 Inhibitors |
| title_fullStr | Systematic Review and Network Meta-Analysis on Treating Hormone Receptor-Positive Metastatic Breast Cancer After CDK4/6 Inhibitors |
| title_full_unstemmed | Systematic Review and Network Meta-Analysis on Treating Hormone Receptor-Positive Metastatic Breast Cancer After CDK4/6 Inhibitors |
| title_short | Systematic Review and Network Meta-Analysis on Treating Hormone Receptor-Positive Metastatic Breast Cancer After CDK4/6 Inhibitors |
| title_sort | systematic review and network meta analysis on treating hormone receptor positive metastatic breast cancer after cdk4 6 inhibitors |
| topic | metastatic breast cancer CDK4/6 inhibitor hormone receptor-positive cancer SERD HER2-low breast cancer AKT inhibitor |
| url | https://www.mdpi.com/1718-7729/32/1/53 |
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