A first-of-its-kind case study published in the Annals of Internal Medicine details the remarkable response of a patient with heavily pre-treated, metastatic prostate cancer to trastuzumab deruxtecan (T-DXd). The study, conducted by researchers at the George Washington University and the Washington DC Veterans Affairs Medical Center, suggests a potential new treatment avenue for aggressive prostate cancer expressing HER2.
The 60-year-old Air Force veteran, diagnosed with stage four metastatic prostate cancer, had exhausted multiple lines of standard therapy and was experiencing progressive disease. As a final attempt, researchers tested the patient's tumor for HER2 expression using immunohistochemistry, which yielded positive results. Consequently, the patient was treated off-label with T-DXd in February 2024.
Significant Tumor Reduction Observed
After four cycles of T-DXd, the patient exhibited a 57% reduction in overall tumor volume, including metastases in the brain. This response defied the initial prognosis, which had suggested hospice care due to the lack of effective treatment options. As of November 2024, the patient continues to do well clinically, having been on T-DXd therapy for nine months, a period significantly longer than the three to four months of efficacy seen with prior lines of treatment.
Implications for HER2 Testing and Targeted Therapy
"This case highlights the promising potential of T-DXd in treating prostate cancer patients, particularly in aggressive forms," stated Maneesh Jain, lead researcher and oncologist at the GW School of Medicine and Health Sciences and attending physician at the Washington DC VA Medical Center. "It also underscores the importance of routine HER2 expression testing in advanced prostate cancer, which could help identify more patients who might benefit from targeted therapies like T-DXd."
The findings suggest that HER2 expression may be a viable therapeutic target in a subset of prostate cancers. While T-DXd is FDA-approved for various HER2-expressing solid tumors, including breast cancer, its use in prostate cancer has not been previously studied. This case report provides initial evidence supporting further investigation of T-DXd in this setting.
Future Directions
Further research is needed to determine the prevalence of HER2 overexpression in advanced prostate cancer and to evaluate the efficacy and safety of T-DXd in larger clinical trials. This case study provides a compelling rationale for exploring HER2-targeted therapies in patients with limited treatment options.
