Abstract P2-08-08: A phase 1 study of RAD1901, an oral selective estrogen receptor degrader, to determine changes in the 18F-FES uptake and tumor responses in ER-positive, HER2-negative, advanced breast cancer patients

Abstract

Abstract Approximately 75% of the tumors from breast cancer patients express the estrogen receptor (ER) at diagnosis. Since patients with ER-positive tumors respond to endocrine therapy, determination of the ER status of a patient has important consequences for treatment decision making. The current standard practice to assess ER status is by using immunohistochemical staining of a tumor biopsy. However, the ability to collect serial tumor biopsies during treatment to determine a patient's response to endocrine therapy is limited by the feasibility of performing multiple biopsies. 18F-fluoroestradiol positron emission tomography (FES-PET) is an imaging modality which can measure ER levels based on FES uptake and has been previously utilized to assess patients' response to endocrine therapies. Serial imaging of tumor FES uptake during treatment with the selective ER degrader (SERD) fulvestrant, demonstrated that significant residual FES uptake in tumor lesions was associated with early disease progression in patients with metastatic breast cancer (van Kruchten et al, Cancer Discov2015;5:72-81). RAD1901 is a novel, orally available SERD that binds to both ER mutant and wild type forms leading to ER degradation in preclinical models of breast cancer. A prior clinical study of RAD1901 in healthy postmenopausal women demonstrated decreased FES uptake in the uterus after RAD1901 treatment, further supporting the hypothesis that FES-PET imaging can provide an early indication of target effect with this agent. RAD1901-106 is a Phase 1 study of RAD1901 in metastatic breast cancer patients to explore the use of FES-PET imaging as an early indicator of clinical response to RAD1901 treatment. Key inclusion criteria include postmenopausal patients with advanced ER-positive, HER2-negative breast cancer, who have received ≤ 3 prior line of endocrine therapy in the metastatic setting. Serial FES-PET imaging performed pre-treatment and after 14 days on therapy is used to evaluate the effect of RAD1901 treatment on the availability of ER binding sites in tumor lesions. Patients may continue on RAD1901 therapy until tumor progression. Patient enrollment started in early 2016 and is ongoing. FES-PET tumor imaging and preliminary clinical data from patients enrolled in the study will be presented. ClinicalTrials.gov identifier: NCT02650817. Citation Format: de Vries EGE, Venema CM, Glaudemans AWJM, Jager A, Garner F, O'Neill A, Patki A, Menke-van der Houven van Oordt CW. A phase 1 study of RAD1901, an oral selective estrogen receptor degrader, to determine changes in the 18F-FES uptake and tumor responses in ER-positive, HER2-negative, advanced breast cancer patients [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-08-08.