Findings from an early phase clinical trial show that patritumab deruxtecan (HER3-DXd) is promising in heavily pretreated patients with HER3-expressing breast cancer. The results of the study were presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting.1
What is HER3?
HER3 (human epidermal growth factor 3) is a small protein receptor on the surface of some cancer cells. When HER3 is "turned on" it causes the cells to grow and reproduce. HER3 belongs to the HER family of receptors which includes HER1/EGFR/erbB1, HER2/erbB2, and HER4/erbB4. HER3 alone lacks or has minimal cancer-causing activity but frequently works with other receptor tyrosine kinases in cancer cells to activate facilitate cancer cell growth. HER3 is expressed in more than 30% of breast cancers
Elevated expression of HER3 has been observed in a wide variety of human cancers and is associated with a worse survival. Research implicates HER3 activation as a major cause of treatment failure in cancer therapy.
About Patritumab deruxtecan (HER3-DXd)
Patritumab deruxtecan is a type of medication known as an Antibody Drug Conjugate. It is comprised of 3 components: an anti-HER3 monoclonal antibody, patritumab, that is linked (connected) to a chemotherapy (topoisomerase I inhibitor0 payload, and an exatecan derivative, through a tetrapeptide-based cleavable linker. The ADC targets the HER3 receptor and delivers the chemotherapy payload to destroy the cancer cell.
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Patritumab was initially evaluated in 182 patients with HER3-expressing metastatic breast cancer that had failed at least 2 prior treatments. Responses to treatment were observed in 22% to 43% of triple negative and HER2 positive cancers over expressing HER3.
The most common side effects were decreased neutrophil count, decreased platelet count, and anemia. Twelve patients also experienced treatment-related interstitial lung disease.
HER3-DXd is currently being developed for the treatment of advanced breast cancer and metastatic or locally advanced EGFR-mutated non-small cell lung cancer where disease has progressed on or after treatment with a third-generation tyrosine kinase inhibitor and platinum-based chemotherapy.
- Amin D.N., Campbell M.R., Moasser M.M. The role of HER3, the unpretentious member of the HER family, in cancer biology and cancer therapeutics. Semin Cell Dev Biol. 2010;21:944–950.