A new case report published in Annals of Internal Medicine describes the success of human epidermal growth factor receptor 2 (HER2) antibody-drug conjugate trastuzumab deruxtecan (T-DXd) in a patient with HER2-expressing treatment-emergent neuroendocrine prostate cancer (t-NEPC).
Researchers from Washington DC VA Medical Center and The George Washington University detail the case of a 60-year-old Air Force Veteran diagnosed with high-volume metastatic prostate cancer in March of 2019. He was first treated with androgen-deprivation therapy and docetaxel, but tumor progression occurred. He received six additional therapies, including participation in three clinical trials, over the course of four years. His response to all treatments was short-lived and followed by rapid disease progression, and he subsequently developed brain metastases. Tissue biopsy confirmed the patient now had t-NEPC, and testing for HER2 by immunohistochemistry showed a strong expression in both his prostate tumor and brain metastasis. In February 2024, he started off-label treatment with T-DXd. After 4 cycles, a 57% overall reduction in tumor volume was seen across sites, including the brain. His clinical status improved significantly despite being told several months before starting T-DXd that he should transition to hospice care due to a lack of treatment options. The case suggests that T-DXd has anti-tumor activity in HER2-expressing mCRPC, including aggressive subtypes like t-NEPC. The researchers also note that this case highlights the need for testing HER2 expression using immunohistochemistry, which is not routinely done for patients with advanced prostate cancer to better identify patients who might benefit from T-DXd treatment. As of October 2024, the patient is clinically doing well.
