An overview of the preclinical discovery and development of trastuzumab deruxtecan: a novel gastric cancer therapeutic.
James KalmukDan RinderCarl HeltzelAlbert Craig LockhartPublished in: Expert opinion on drug discovery (2022)
While the 2010 ToGA trial demonstrated efficacy of trastuzumab in HER2 positive gastric cancer, subsequent trials of HER2-directed therapy have disappointed. Downregulation of HER2 after trastuzumab may play a role; however, trastuzumab deruxtecan maintains some efficacy in low-level HER2 expressing tumors. The DESTINY-Gastric01 cohort was from South Korea/Japan; authors have reported differences in gastric cancer risk factors/physiology between Eastern and Western populations. DESTINY-Gastric02 will evaluate trastuzumab deruxtecan in Western patients to confirm generalizability. Pulmonary side effects are notable;physicians must be cognizant of overlapping toxicities with combination therapy.
Keyphrases
- epidermal growth factor receptor
- metastatic breast cancer
- combination therapy
- risk factors
- end stage renal disease
- south africa
- tyrosine kinase
- ejection fraction
- newly diagnosed
- chronic kidney disease
- clinical trial
- primary care
- small molecule
- peritoneal dialysis
- pulmonary hypertension
- prognostic factors
- high throughput
- patient reported outcomes
- mesenchymal stem cells
- phase iii
- phase ii
- smoking cessation