Abstract PO5-07-11: Use of 64Cu-DOTA trastuzumab -PET to predict response to trastuzumab-deruxtecan (TDXd) in patients with metastatic disease to the brain: Study in Progress

Abstract Background: We have utilized 64Cu-DOTA trastuzumab-PET imaging in patients with advanced breast cancer. In our experience, uptake on 64Cu-DOTA trastuzumab-PET correlated with the qualitative assessment of HER2 by IHC. In women treated with the antibody-drug conjugate (ADC), ado-trastuzumab emtansine (TDM1), we identified a threshold level of 64Cu-DOTA trastuzumab-PET uptake that predicted for lack of response to TDM1. As patients are living longer with advanced breast cancer, the incidence of brain metastasis has increased. The ADC, trastuzumab-deruxtecan (T-DXd) has demonstrated activity in patients with metastatic HER2 positive breast cancer with brain metastases. The DESTINY 04 trial included patients with HER2 1+ and 2+ disease and demonstrated superior survival compared to standard of care. It is not feasible to biopsy all brain metastases to determine tumor markers. Given the increased incidence of brain metastases in this population and the efficacy of T-DXd in patients with HER2+ metastatic disease to the brain, we initiated a study of 64Cu-DOTA trastuzumab-PET/MRI of the brain prior to institution of T-Dxd. Endpoints Primary: 1. 64Cu-DOTA-trastuzumab PET-CT will identify tumor heterogeneity of trastuzumab uptake in women with metastatic breast cancers. 2. The degree of uptake of 64Cu-DOTA-trastuzumab PET-CT will predict for response to Enhertu. Secondary: 1. Uptake of 64Cu-DOTA-trastuzumab PET-CT will be predictive of response duration to Enhertu. Eligibility: Patients must have documented recurrent breast cancer that is HER2 1+, 2+ or 3+, evidence of brain metastases by CT or MRI of the brain and are candidate for treatment with trastuzumab-deruxtecan. The CNS disease must be stable and not in need of intervention. Methods: Prior to treatment staging workups includes pathologic review of HER2 status, disease staging with 18FDG-PET or CT of the chest/abdomen/pelvis and bone scan, and 64Cu-DOTA-trastuzumab PET/MRI of the brain. After initiation of T-Dxd, MRI of the brain is repeated every 6 weeks for the first 24 weeks and every 9 weeks thereafter. Progress: We have enrolled 1 patients to date, received PET and dynamic contrast-enhanced MRI. Four lesions were analyzed in this patient. The mean values of Ktrans (volumetric perfusion to tumor, s−1) in these lesions near a prior resection cavity were 0.210 s−1, indicating sufficient perfusion for ADC uptake. Corresponding to this perfusion data, the mean SUVmax of these lesions on the 64Cu-DOTA-trastuzumab PET scans was 5.38. Citation Format: Joanne Mortimer, Kofi Poku, Jessica Liu, Russell Rockne, Chen Bihong, Ryan Woodall, Vikram Adhikarla. Use of 64Cu-DOTA trastuzumab -PET to predict response to trastuzumab-deruxtecan (TDXd) in patients with metastatic disease to the brain: Study in Progress abstract. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-07-11.