Timing of Dose Reductions and Survival Outcomes in Metastatic Breast Cancer Patients Treated with Cyclin-Dependent Kinase 4/6 Inhibitors
Background/Objectives: Dose reductions in CDK4/6 inhibitors, such as ribociclib and palbociclib, are often necessary due to treatment-related toxicities in patients with advanced breast cancer. This study aims to evaluate the impact of the timing of dose reductions on progression-free survival (PFS)...
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MDPI AG
2024-11-01
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| Series: | Current Oncology |
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| Online Access: | https://www.mdpi.com/1718-7729/31/12/548 |
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| author | Pınar Kubilay Tolunay Bediz Kurt İnci Şura Usta Ali Topkaç Berkan Karabuğa Ergin Aydemir İrem Öner Büşra Akay Hacan Öztürk Ateş Cengiz Karaçin Ülkü Yalçıntaş Arslan |
| author_facet | Pınar Kubilay Tolunay Bediz Kurt İnci Şura Usta Ali Topkaç Berkan Karabuğa Ergin Aydemir İrem Öner Büşra Akay Hacan Öztürk Ateş Cengiz Karaçin Ülkü Yalçıntaş Arslan |
| author_sort | Pınar Kubilay Tolunay |
| collection | DOAJ |
| description | Background/Objectives: Dose reductions in CDK4/6 inhibitors, such as ribociclib and palbociclib, are often necessary due to treatment-related toxicities in patients with advanced breast cancer. This study aims to evaluate the impact of the timing of dose reductions on progression-free survival (PFS) and overall survival (OS) in a real-world cohort. Methods: This single-center, retrospective study included patients treated with ribociclib or palbociclib between 2019 and 2023 at a cancer center in Turkey. Dose reductions due to drug-related toxicities were recorded, and survival outcomes were analyzed. Patients were categorized based on the timing of dose reductions: within the first 3 months (early) and after 3 months (late). Results: Among 392 patients (mean age 57.13 years), 16.8% had dose reductions within 3 months, 21.7% had late dose reductions, and 61.5% had no dose reductions. The mPFS was 14.26 months for early dose reductions, 33.12 months for late dose reductions, and 20.6 months for no dose reductions (<i>p</i> < 0.001). The mOS was 37.12 months for early dose reductions, not reached for late dose reductions, and 57.76 months for no dose reductions (<i>p</i> < 0.001). Hematological toxicity, primarily neutropenia, was the most common cause of dose reductions. The ECOG performance status, line of therapy, and CDK4/6 inhibitor type were also significant predictors of PFS and OS. Conclusions: Early dose reductions in CDK4/6 inhibitors negatively affect PFS and OS, highlighting the importance of maintaining treatment intensity in the first 3 months. However, late dose reductions do not negatively affect progression-free survival (PFS) or overall survival (OS), with late dose reductions associated with better outcomes. Prospective studies in larger patient populations will further clarify our knowledge on this subject. |
| format | Article |
| id | doaj-art-a9d0a88a93f74986b58a422fae315640 |
| institution | Kabale University |
| issn | 1198-0052 1718-7729 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Current Oncology |
| spelling | doaj-art-a9d0a88a93f74986b58a422fae3156402024-12-27T14:19:56ZengMDPI AGCurrent Oncology1198-00521718-77292024-11-0131127426743610.3390/curroncol31120548Timing of Dose Reductions and Survival Outcomes in Metastatic Breast Cancer Patients Treated with Cyclin-Dependent Kinase 4/6 InhibitorsPınar Kubilay Tolunay0Bediz Kurt İnci1Şura Usta2Ali Topkaç3Berkan Karabuğa4Ergin Aydemir5İrem Öner6Büşra Akay Hacan7Öztürk Ateş8Cengiz Karaçin9Ülkü Yalçıntaş Arslan10Department of Medical Oncology, Ankara University School of Medicine, Ankara 06590, TurkeyDepartment of Medical Oncology, Dr. Abdurrahman Yurtaslan Oncology Training and Research Hospital, University of Health Sciences, Ankara 06200, TurkeyDepartment of Medical Oncology, Dr. Abdurrahman Yurtaslan Oncology Training and Research Hospital, University of Health Sciences, Ankara 06200, TurkeyDepartment of Medical Oncology, Dr. Abdurrahman Yurtaslan Oncology Training and Research Hospital, University of Health Sciences, Ankara 06200, TurkeyDepartment of Medical Oncology, Dr. Abdurrahman Yurtaslan Oncology Training and Research Hospital, University of Health Sciences, Ankara 06200, TurkeyDepartment of Medical Oncology, Dr. Abdurrahman Yurtaslan Oncology Training and Research Hospital, University of Health Sciences, Ankara 06200, TurkeyDepartment of Medical Oncology, Dr. Abdurrahman Yurtaslan Oncology Training and Research Hospital, University of Health Sciences, Ankara 06200, TurkeyDepartment of Medical Oncology, Dr. Abdurrahman Yurtaslan Oncology Training and Research Hospital, University of Health Sciences, Ankara 06200, TurkeyDepartment of Medical Oncology, Dr. Abdurrahman Yurtaslan Oncology Training and Research Hospital, University of Health Sciences, Ankara 06200, TurkeyDepartment of Medical Oncology, Dr. Abdurrahman Yurtaslan Oncology Training and Research Hospital, University of Health Sciences, Ankara 06200, TurkeyDepartment of Medical Oncology, Dr. Abdurrahman Yurtaslan Oncology Training and Research Hospital, University of Health Sciences, Ankara 06200, TurkeyBackground/Objectives: Dose reductions in CDK4/6 inhibitors, such as ribociclib and palbociclib, are often necessary due to treatment-related toxicities in patients with advanced breast cancer. This study aims to evaluate the impact of the timing of dose reductions on progression-free survival (PFS) and overall survival (OS) in a real-world cohort. Methods: This single-center, retrospective study included patients treated with ribociclib or palbociclib between 2019 and 2023 at a cancer center in Turkey. Dose reductions due to drug-related toxicities were recorded, and survival outcomes were analyzed. Patients were categorized based on the timing of dose reductions: within the first 3 months (early) and after 3 months (late). Results: Among 392 patients (mean age 57.13 years), 16.8% had dose reductions within 3 months, 21.7% had late dose reductions, and 61.5% had no dose reductions. The mPFS was 14.26 months for early dose reductions, 33.12 months for late dose reductions, and 20.6 months for no dose reductions (<i>p</i> < 0.001). The mOS was 37.12 months for early dose reductions, not reached for late dose reductions, and 57.76 months for no dose reductions (<i>p</i> < 0.001). Hematological toxicity, primarily neutropenia, was the most common cause of dose reductions. The ECOG performance status, line of therapy, and CDK4/6 inhibitor type were also significant predictors of PFS and OS. Conclusions: Early dose reductions in CDK4/6 inhibitors negatively affect PFS and OS, highlighting the importance of maintaining treatment intensity in the first 3 months. However, late dose reductions do not negatively affect progression-free survival (PFS) or overall survival (OS), with late dose reductions associated with better outcomes. Prospective studies in larger patient populations will further clarify our knowledge on this subject.https://www.mdpi.com/1718-7729/31/12/548CDK4/6 inhibitorsbreast cancerdose reductionsurvival outcomes |
| spellingShingle | Pınar Kubilay Tolunay Bediz Kurt İnci Şura Usta Ali Topkaç Berkan Karabuğa Ergin Aydemir İrem Öner Büşra Akay Hacan Öztürk Ateş Cengiz Karaçin Ülkü Yalçıntaş Arslan Timing of Dose Reductions and Survival Outcomes in Metastatic Breast Cancer Patients Treated with Cyclin-Dependent Kinase 4/6 Inhibitors Current Oncology CDK4/6 inhibitors breast cancer dose reduction survival outcomes |
| title | Timing of Dose Reductions and Survival Outcomes in Metastatic Breast Cancer Patients Treated with Cyclin-Dependent Kinase 4/6 Inhibitors |
| title_full | Timing of Dose Reductions and Survival Outcomes in Metastatic Breast Cancer Patients Treated with Cyclin-Dependent Kinase 4/6 Inhibitors |
| title_fullStr | Timing of Dose Reductions and Survival Outcomes in Metastatic Breast Cancer Patients Treated with Cyclin-Dependent Kinase 4/6 Inhibitors |
| title_full_unstemmed | Timing of Dose Reductions and Survival Outcomes in Metastatic Breast Cancer Patients Treated with Cyclin-Dependent Kinase 4/6 Inhibitors |
| title_short | Timing of Dose Reductions and Survival Outcomes in Metastatic Breast Cancer Patients Treated with Cyclin-Dependent Kinase 4/6 Inhibitors |
| title_sort | timing of dose reductions and survival outcomes in metastatic breast cancer patients treated with cyclin dependent kinase 4 6 inhibitors |
| topic | CDK4/6 inhibitors breast cancer dose reduction survival outcomes |
| url | https://www.mdpi.com/1718-7729/31/12/548 |
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