Trastuzumab emtansine (Kadcyla), an antibody-drug conjugate of trastuzumab (Herceptin) connected by a thioether linker to the microtubule inhibitor DM1 (a cytotoxic derivative of maytansine), provides direct intracellular delivery of the potent cytotoxin DM1 to HER2-overexpressing cells, while retaining trastuzumab activity. Its approval in metastatic/advanced breast cancer (BC) has been extended to include single-agent adjuvant treatment of HER2-positive early BC in patients with residual invasive disease in the breast and/or lymph nodes after neoadjuvant taxane-based and HER2-targeted treatment. In the pivotal KATHERINE trial in this population, significantly more trastuzumab emtansine than trastuzumab recipients were estimated to be free of invasive disease recurrence at 3 years, with a 50% reduction in the risk of invasive disease recurrence or death. The tolerability of trastuzumab emtansine in early BC was consistent with its known safety profile; as expected, adverse events were more common with trastuzumab emtansine than with trastuzumab. Recently updated international and national treatment guidelines recommend trastuzumab emtansine as a preferred option in this high-risk BC population.
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http://dx.doi.org/10.1007/s40265-020-01408-7 | DOI Listing |
Cancer Chemother Pharmacol
December 2024
Departments of Pharmacology, Medicine Faculty, Sivas Cumhuriyet University, Sivas, Türkiye.
Purpose: Human epidermal growth factor-2 (HER-2) targeted drugs are used in only HER-2 overexpressed cancers. However, only a small portion of these cancer types are HER-2 overexpressed. In this study, we aimed to upregulate HER-2 receptors in MCF-7 breast cancer and HT-29 colon cancer cell cultures, which these cells are not HER-2 upregulated in natural status.
View Article and Find Full Text PDFTher Adv Drug Saf
December 2024
The Center of Breast Disease Diagnosis and Treatment of Affiliated Hospital of Qinghai University and Affiliated Cancer Hospital of Qinghai University, No. 29 Tongren Road, Xining, Qinghai 810000, China.
Background: Antibody-drug conjugates (ADCs), as a new type of targeted drug, have been widely used in breast cancer patients in recent years. However, while achieving better efficacy, its hepatotoxicity should not be ignored.
Objectives: To clarify the incidence of hepatotoxicity associated with ADCs and compare the incidence of hepatotoxicity of ADCs with different drugs.
Cancers (Basel)
December 2024
Phase IV Clinical Studies Unit, IRCCS Regina Elena National Cancer Institute, 00144 Rome, Italy.
Background/objectives: HER2-positive breast cancer (HER2BC) is an aggressive subtype, with neoadjuvant treatment (NAT) aiming to achieve a pathological complete response (pCR) to improve long-term outcomes. Trastuzumab emtansine (T-DM1) has been established as the standard of care in the adjuvant setting for HER2BC patients who do not obtain pCR. The ATD study aimed to evaluate the real-world tolerability of T-DM1 in this setting.
View Article and Find Full Text PDFCancers (Basel)
December 2024
Oncology Unit, "Dario Camberlingo" Hospital, 72021 Francavilla Fontana, Italy.
Antibody-drug conjugates (ADCs) have revolutionized the treatment landscape for metastatic breast cancer, offering targeted delivery of cytotoxic agents with improved efficacy and tolerability compared to conventional chemotherapy. This narrative review explores key predictive factors influencing the efficacy of ADCs, focusing on HER2-targeted therapies, such as trastuzumab emtansine and trastuzumab deruxtecan, as well as sacituzumab govitecan for triple-negative breast cancer. HER2 expression, TROP-2 levels, hormone receptor status, and the tumor microenvironment emerge as critical biomarkers for patient selection and therapeutic outcomes.
View Article and Find Full Text PDFExpert Opin Drug Saf
December 2024
Guangdong Provincial Biotechnology Research Institute (Guangdong Provincial Laboratory Animals Monitoring Center), Guangzhou, Guangdong, China.
Background: The cardiovascular risk profiles of trastuzumab drug conjugates (T-DCs) in the treatment of Human Epidermal Growth Factor Receptor 2 (HER2)-positive breast cancer are uncertain. This study analyzed real-world adverse events data from the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) to investigate the association between T-DCs and major adverse cardiovascular events (MACE).
Methods: We searched the FAERS database for reports of cardiovascular adverse events in patients with HER2-positive breast cancer receiving trastuzumab, ado-trastuzumab emtansine (T-DM1), and trastuzumab deruxtecan (T-Dxd).
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