Sequencing Antibody Drug Conjugates in Breast Cancer: Exploring Future Roles
Antibody drug conjugates (ADCs) have emerged as a highly effective treatment strategy across breast cancer (BC) subtypes, including human epidermal growth factor receptor 2-positive (HER2+), hormone-receptor positive (ER/PR+), and triple-negative breast cancer (TNBC). Over the past twenty years, ADC...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-11-01
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| Series: | Current Oncology |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1718-7729/30/12/743 |
| _version_ | 1827575097552011264 |
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| author | Mary Anne Fenton Paolo Tarantino Stephanie L. Graff |
| author_facet | Mary Anne Fenton Paolo Tarantino Stephanie L. Graff |
| author_sort | Mary Anne Fenton |
| collection | DOAJ |
| description | Antibody drug conjugates (ADCs) have emerged as a highly effective treatment strategy across breast cancer (BC) subtypes, including human epidermal growth factor receptor 2-positive (HER2+), hormone-receptor positive (ER/PR+), and triple-negative breast cancer (TNBC). Over the past twenty years, ADCs have undergone relevant evolutions, from target diversity to payload ratio, to linker design, allowing for a progressive increase in their efficacy. From the first-generation ADC, trastuzumab emtansine (T-DM1), approved in 2013 for HER2+ breast cancer, to next generation ADCs such as sacituzumab govitecan and trastuzumab deruxtecan, to emerging ADCs on the horizon, we continue to see unparalleled efficacy compared to traditional chemotherapy. However, each ADC has brought a new cadre of adverse events for clinicians and patients to manage. Importantly, with the development and approval of several ADCs to treat metastatic breast cancer, there are unanswered clinical questions surrounding how to optimally sequence treatment for patients who may be candidates for more than one ADC and, in general, how to treat patients beyond progression on ADCs. From bench to bedside, in this review, we will discuss the pharmacology and current indications for the novel ADCs trastuzumab deruxtecan and sacituzumab govitecan. Highlighting emerging ADCs and ongoing clinical trials, we will anticipate the changes in the breast cancer treatment paradigm. Lastly, we will outline the available data and current approaches for adverse event management and sequencing strategies for ADCs in clinical practice, including proposed mechanisms of resistance. |
| first_indexed | 2024-03-08T20:51:22Z |
| format | Article |
| id | doaj.art-11ae706ced044892a413cd9ac79afd1b |
| institution | Directory Open Access Journal |
| issn | 1198-0052 1718-7729 |
| language | English |
| last_indexed | 2024-03-08T20:51:22Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Current Oncology |
| spelling | doaj.art-11ae706ced044892a413cd9ac79afd1b2023-12-22T14:02:20ZengMDPI AGCurrent Oncology1198-00521718-77292023-11-013012102111022310.3390/curroncol30120743Sequencing Antibody Drug Conjugates in Breast Cancer: Exploring Future RolesMary Anne Fenton0Paolo Tarantino1Stephanie L. Graff2Legorreta Cancer Center, Brown University, Providence, RI 02903, USAMedical Oncology, Dana Farber Cancer Institute, Boston, MA 02215, USALegorreta Cancer Center, Brown University, Providence, RI 02903, USAAntibody drug conjugates (ADCs) have emerged as a highly effective treatment strategy across breast cancer (BC) subtypes, including human epidermal growth factor receptor 2-positive (HER2+), hormone-receptor positive (ER/PR+), and triple-negative breast cancer (TNBC). Over the past twenty years, ADCs have undergone relevant evolutions, from target diversity to payload ratio, to linker design, allowing for a progressive increase in their efficacy. From the first-generation ADC, trastuzumab emtansine (T-DM1), approved in 2013 for HER2+ breast cancer, to next generation ADCs such as sacituzumab govitecan and trastuzumab deruxtecan, to emerging ADCs on the horizon, we continue to see unparalleled efficacy compared to traditional chemotherapy. However, each ADC has brought a new cadre of adverse events for clinicians and patients to manage. Importantly, with the development and approval of several ADCs to treat metastatic breast cancer, there are unanswered clinical questions surrounding how to optimally sequence treatment for patients who may be candidates for more than one ADC and, in general, how to treat patients beyond progression on ADCs. From bench to bedside, in this review, we will discuss the pharmacology and current indications for the novel ADCs trastuzumab deruxtecan and sacituzumab govitecan. Highlighting emerging ADCs and ongoing clinical trials, we will anticipate the changes in the breast cancer treatment paradigm. Lastly, we will outline the available data and current approaches for adverse event management and sequencing strategies for ADCs in clinical practice, including proposed mechanisms of resistance.https://www.mdpi.com/1718-7729/30/12/743breast cancerantibody drug conjugatestrastuzumab deruxtecansacituzumab govitecanHER2-lowHER2+ |
| spellingShingle | Mary Anne Fenton Paolo Tarantino Stephanie L. Graff Sequencing Antibody Drug Conjugates in Breast Cancer: Exploring Future Roles Current Oncology breast cancer antibody drug conjugates trastuzumab deruxtecan sacituzumab govitecan HER2-low HER2+ |
| title | Sequencing Antibody Drug Conjugates in Breast Cancer: Exploring Future Roles |
| title_full | Sequencing Antibody Drug Conjugates in Breast Cancer: Exploring Future Roles |
| title_fullStr | Sequencing Antibody Drug Conjugates in Breast Cancer: Exploring Future Roles |
| title_full_unstemmed | Sequencing Antibody Drug Conjugates in Breast Cancer: Exploring Future Roles |
| title_short | Sequencing Antibody Drug Conjugates in Breast Cancer: Exploring Future Roles |
| title_sort | sequencing antibody drug conjugates in breast cancer exploring future roles |
| topic | breast cancer antibody drug conjugates trastuzumab deruxtecan sacituzumab govitecan HER2-low HER2+ |
| url | https://www.mdpi.com/1718-7729/30/12/743 |
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