EA1211: interim FDG-PET/CT for predicting response of HER2-positive breast cancer to neoadjuvant therapy (DIRECT trial)
The EA1211/DIRECT trial is investigating whether FDG-PET/CT imaging performed shortly after starting treatment can predict tumor response in early-stage HER2-positive breast cancer patients. Read more about the trial design and its key objectives in this Clinical Trial Protocol published in our partner journal Future Oncology.
Abstract
Recent studies indicate that early changes on 2-deoxy-2-[18F]fluoro-D-glucose Positron Emission Tomography/Computed Tomography (FDG-PET/CT) predict response to human epidermal growth factor receptor 2 (HER2)-directed therapy. EA1211/DIRECT is a multicenter, single-arm, primary imaging Phase II study enrolling patients with Stage II/III HER2-positive breast cancer receiving pertuzumab-based neoadjuvant therapy followed by surgery. The trial aims to validate FDG-PET/CT as a neoadjuvant interim (niFDG-PET/CT) imaging integral biomarker in patients treated with standard HER2-directed regimens. The primary objective is to estimate the negative predictive value of niFDG-PET/CT for pathologic complete response using delta maximum standardized uptake value corrected for lean body mass day 15 (ΔSULmaxD15) of the primary breast cancer at a threshold of 40%. If EA1211/DIRECT meets its objectives, the results will be used to design clinical utility studies for this noninvasive imaging biomarker, hoping to change practice toward a response-guided approach, ensuring patients receive treatment tailored to their tumor biology and individual response.
Clinical trial registration
NCT05710328.
Plain Language Summary
Early-stage HER2-positive breast cancer is a subset of breast cancer that is usually treated with a combination of chemotherapy and HER2-targeted therapy before surgery, with the aim of shrinking down the tumor to provide a cure. The standard treatment involves several different drugs and is often linked to side effects. We want to find a way to figure out early in the treatment course if the treatment is working well to make better decisions for patients. The EA1211/DIRECT trial is testing whether a special type of imaging test, called FDG-PET/CT, 2–3 weeks after starting standard cancer treatment will help predict how breast cancer will shrink or respond by the time of surgery. FDG is a radioactive sugar-based tracer that is given in a vein before PET/CT imaging, which helps doctors see areas with active cancer. PET and CT scans are imaging techniques that make detailed pictures of areas inside the body. EA1211/DIRECT aims to find out if FDG-PET/CT can be used to make more personalized decisions around treatment for patients with HER2-positive breast cancer. The use of FDG-PET/CT may help doctors decide if a patient needs more or less treatment before surgery to achieve the best outcome. Overall, this study looks at whether FDG-PET/CT is useful in predicting how well patients will respond to standard chemotherapy treatments.