Progression-Free Survival and Overall Survival of CDK 4/6 Inhibitors Plus Endocrine Therapy in Metastatic Breast Cancer: A Systematic Review and Meta-Analysis
The introduction of CDK4/6 inhibitors in combination with endocrine therapy (ET) represents the most relevant advance in the management of hormone receptor (HR) positive, HER2-negative metastatic breast cancer over the last few years. This meta-analysis of randomized controlled trials (RCTs) is aime...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/17/6400 |
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| author | Michela Piezzo Paolo Chiodini Maria Riemma Stefania Cocco Roberta Caputo Daniela Cianniello Germira Di Gioia Vincenzo Di Lauro Francesca Di Rella Giuseppina Fusco Giovanni Iodice Francesco Nuzzo Carmen Pacilio Matilde Pensabene Michelino De Laurentiis |
| author_facet | Michela Piezzo Paolo Chiodini Maria Riemma Stefania Cocco Roberta Caputo Daniela Cianniello Germira Di Gioia Vincenzo Di Lauro Francesca Di Rella Giuseppina Fusco Giovanni Iodice Francesco Nuzzo Carmen Pacilio Matilde Pensabene Michelino De Laurentiis |
| author_sort | Michela Piezzo |
| collection | DOAJ |
| description | The introduction of CDK4/6 inhibitors in combination with endocrine therapy (ET) represents the most relevant advance in the management of hormone receptor (HR) positive, HER2-negative metastatic breast cancer over the last few years. This meta-analysis of randomized controlled trials (RCTs) is aimed to better characterize the efficacy of CDK4/6 inhibitors in some relevant subgroups and to test heterogeneity between different compounds with a particular focus on their ability to improve overall survival (OS). Pooled estimates of hazard ratios (HRs) were computed for progression-free survival (PFS), OS, and objective response rate (ORR) analysis in predefined subgroups to better understand treatment effect concerning specific patients’ characteristics. To estimate the absolute benefit in terms of PFS, pooled survival curves were generated by pooling the data of all trials. A total of eight RCTs were included. Adding a CDK4/6 inhibitor to ET is beneficial in terms of PFS, irrespective of the presence or not of visceral metastases, the number of metastatic sites, and the length of the treatment-free interval (TFI). The addition of CDK4/6 inhibitors produces a significant OS improvement, both in aromatase inhibitor (AI)-sensitive (HR 0.75, 95% CI) and AI-resistant patients (HR 0.77, 95% CI [0.67–0.89]). Pooled data from each single drug show that palbociclib remains the only class member not showing a statistically significant HR for OS (HR 0.83, 95% CI [0.68–1.02]). |
| first_indexed | 2024-03-10T16:36:52Z |
| format | Article |
| id | doaj.art-764be9bb2233436e98198bfaa49cc350 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T16:36:52Z |
| publishDate | 2020-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-764be9bb2233436e98198bfaa49cc3502023-11-20T12:23:45ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-09-012117640010.3390/ijms21176400Progression-Free Survival and Overall Survival of CDK 4/6 Inhibitors Plus Endocrine Therapy in Metastatic Breast Cancer: A Systematic Review and Meta-AnalysisMichela Piezzo0Paolo Chiodini1Maria Riemma2Stefania Cocco3Roberta Caputo4Daniela Cianniello5Germira Di Gioia6Vincenzo Di Lauro7Francesca Di Rella8Giuseppina Fusco9Giovanni Iodice10Francesco Nuzzo11Carmen Pacilio12Matilde Pensabene13Michelino De Laurentiis14Department of Breast and Thoracic Oncology, Division of Breast Medical Oncology, Istituto Nazionale Tumori IRCCS “Fondazione G. Pascale”, 80131 Naples, ItalyDepartment of Public, Clinical and Preventive Medicine, Medical Statistics Unit, University of Campania Luigi Vanvitelli, 80138 Naples, ItalyDepartment of Breast and Thoracic Oncology, Division of Breast Medical Oncology, Istituto Nazionale Tumori IRCCS “Fondazione G. Pascale”, 80131 Naples, ItalyDepartment of Breast and Thoracic Oncology, Division of Breast Medical Oncology, Istituto Nazionale Tumori IRCCS “Fondazione G. Pascale”, 80131 Naples, ItalyDepartment of Breast and Thoracic Oncology, Division of Breast Medical Oncology, Istituto Nazionale Tumori IRCCS “Fondazione G. Pascale”, 80131 Naples, ItalyDepartment of Breast and Thoracic Oncology, Division of Breast Medical Oncology, Istituto Nazionale Tumori IRCCS “Fondazione G. Pascale”, 80131 Naples, ItalyDepartment of Breast and Thoracic Oncology, Division of Breast Medical Oncology, Istituto Nazionale Tumori IRCCS “Fondazione G. Pascale”, 80131 Naples, ItalyDepartment of Breast and Thoracic Oncology, Division of Breast Medical Oncology, Istituto Nazionale Tumori IRCCS “Fondazione G. Pascale”, 80131 Naples, ItalyDepartment of Breast and Thoracic Oncology, Division of Breast Medical Oncology, Istituto Nazionale Tumori IRCCS “Fondazione G. Pascale”, 80131 Naples, ItalyDepartment of Breast and Thoracic Oncology, Division of Breast Medical Oncology, Istituto Nazionale Tumori IRCCS “Fondazione G. Pascale”, 80131 Naples, ItalyDepartment of Breast and Thoracic Oncology, Division of Breast Medical Oncology, Istituto Nazionale Tumori IRCCS “Fondazione G. Pascale”, 80131 Naples, ItalyDepartment of Breast and Thoracic Oncology, Division of Breast Medical Oncology, Istituto Nazionale Tumori IRCCS “Fondazione G. Pascale”, 80131 Naples, ItalyDepartment of Breast and Thoracic Oncology, Division of Breast Medical Oncology, Istituto Nazionale Tumori IRCCS “Fondazione G. Pascale”, 80131 Naples, ItalyDepartment of Breast and Thoracic Oncology, Division of Breast Medical Oncology, Istituto Nazionale Tumori IRCCS “Fondazione G. Pascale”, 80131 Naples, ItalyDepartment of Breast and Thoracic Oncology, Division of Breast Medical Oncology, Istituto Nazionale Tumori IRCCS “Fondazione G. Pascale”, 80131 Naples, ItalyThe introduction of CDK4/6 inhibitors in combination with endocrine therapy (ET) represents the most relevant advance in the management of hormone receptor (HR) positive, HER2-negative metastatic breast cancer over the last few years. This meta-analysis of randomized controlled trials (RCTs) is aimed to better characterize the efficacy of CDK4/6 inhibitors in some relevant subgroups and to test heterogeneity between different compounds with a particular focus on their ability to improve overall survival (OS). Pooled estimates of hazard ratios (HRs) were computed for progression-free survival (PFS), OS, and objective response rate (ORR) analysis in predefined subgroups to better understand treatment effect concerning specific patients’ characteristics. To estimate the absolute benefit in terms of PFS, pooled survival curves were generated by pooling the data of all trials. A total of eight RCTs were included. Adding a CDK4/6 inhibitor to ET is beneficial in terms of PFS, irrespective of the presence or not of visceral metastases, the number of metastatic sites, and the length of the treatment-free interval (TFI). The addition of CDK4/6 inhibitors produces a significant OS improvement, both in aromatase inhibitor (AI)-sensitive (HR 0.75, 95% CI) and AI-resistant patients (HR 0.77, 95% CI [0.67–0.89]). Pooled data from each single drug show that palbociclib remains the only class member not showing a statistically significant HR for OS (HR 0.83, 95% CI [0.68–1.02]).https://www.mdpi.com/1422-0067/21/17/6400epidemiologycancermetastatic breast cancerhormone therapyCDK4/6 inhibitorsoverall survival |
| spellingShingle | Michela Piezzo Paolo Chiodini Maria Riemma Stefania Cocco Roberta Caputo Daniela Cianniello Germira Di Gioia Vincenzo Di Lauro Francesca Di Rella Giuseppina Fusco Giovanni Iodice Francesco Nuzzo Carmen Pacilio Matilde Pensabene Michelino De Laurentiis Progression-Free Survival and Overall Survival of CDK 4/6 Inhibitors Plus Endocrine Therapy in Metastatic Breast Cancer: A Systematic Review and Meta-Analysis International Journal of Molecular Sciences epidemiology cancer metastatic breast cancer hormone therapy CDK4/6 inhibitors overall survival |
| title | Progression-Free Survival and Overall Survival of CDK 4/6 Inhibitors Plus Endocrine Therapy in Metastatic Breast Cancer: A Systematic Review and Meta-Analysis |
| title_full | Progression-Free Survival and Overall Survival of CDK 4/6 Inhibitors Plus Endocrine Therapy in Metastatic Breast Cancer: A Systematic Review and Meta-Analysis |
| title_fullStr | Progression-Free Survival and Overall Survival of CDK 4/6 Inhibitors Plus Endocrine Therapy in Metastatic Breast Cancer: A Systematic Review and Meta-Analysis |
| title_full_unstemmed | Progression-Free Survival and Overall Survival of CDK 4/6 Inhibitors Plus Endocrine Therapy in Metastatic Breast Cancer: A Systematic Review and Meta-Analysis |
| title_short | Progression-Free Survival and Overall Survival of CDK 4/6 Inhibitors Plus Endocrine Therapy in Metastatic Breast Cancer: A Systematic Review and Meta-Analysis |
| title_sort | progression free survival and overall survival of cdk 4 6 inhibitors plus endocrine therapy in metastatic breast cancer a systematic review and meta analysis |
| topic | epidemiology cancer metastatic breast cancer hormone therapy CDK4/6 inhibitors overall survival |
| url | https://www.mdpi.com/1422-0067/21/17/6400 |
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