Exploring DESTINY: the Past, Present, and Future of Trastuzumab Deruxtecan.
Azka AliStephanie L GraffPublished in: Current oncology reports (2023)
T-DXd is a novel antibody-drug conjugate (ADC) composed of a humanized IgG1 monoclonal antibody against HER2 receptor bound to a potent topoisomerase I cytotoxin payload by a cleavable peptide linker. It has been shown to have robust preclinical activity in pretreated cancer cell lines, as well as meaningful clinical activity in advanced HER2-expressing breast cancer. Recent studies have demonstrated T-DXd as an active agent for metastatic HER2-positive patients, and as a viable additional line for heavily pretreated patients with HER2-low disease. The toxicity of T-DXd remains manageable and burden of side effects seems to be lower when offered as an earlier line of therapy over the course of treatment. In this review, we discuss the pharmacology of T-DXd, review pertinent preclinical and clinical data, and address potential challenges and future directions related to the use of T-DXd in clinical practice.
Keyphrases
- monoclonal antibody
- end stage renal disease
- clinical practice
- ejection fraction
- cell therapy
- small cell lung cancer
- chronic kidney disease
- squamous cell carcinoma
- newly diagnosed
- oxidative stress
- peritoneal dialysis
- papillary thyroid
- electronic health record
- stem cells
- machine learning
- risk factors
- big data
- binding protein
- bone marrow
- drug delivery
- risk assessment
- human health
- squamous cell
- lymph node metastasis
- case control
- replacement therapy