Early prediction of endocrine responsiveness in ER+/HER2-negative metastatic breast cancer (MBC): Pilot study with 18F-Fluoroestradiol (18F-FES) CT/PET

Background: 18F-FES PET/CT is considered an accurate diagnostic tool to determine whole-body endocrine responsiveness. In the ET-FES trial, we evaluated 18F-FES PET/CT as a predictive tool in ER+/HER2- metastatic breast cancer (MBC). Methods: Eligible patients underwent a 18F-FES PET/CT at baseline. Patients with SUV≥2 received single agent ET until PD; patients with SUV<2 were randomized to single agent ET (Arm A) or chemotherapy (CT) (Arm B). Primary objective was to compare the activity of first line ET versus CT in patients with 18F-FES SUV <2. Results: Overall, 147 patients were enrolled; 117 presented with 18F-FES SUV≥2 and received ET; 30 pts with SUV<2 were randomized to ET or CT. After a median follow up of 62.4 months, 104 patients (73.2%) had disease progression and 53 died (37.3%). Median PFS was 12.4 months (95%CI 3.1-59.6) in patients with SUV <2 randomised to Arm A versus 23.0 months (95%CI 7.7-30.0) in Arm B, (HR = 0.71, 95%CI 0.3 - 1.7); median PFS was 18.0 months (95%CI 11.2-23.1) in patients with SUV≥2 treated with ET. Median OS was 28.2 months (95%CI 14.2-NE) in patients with SUV <2 randomized to ET (Arm A) versus 52.8 months (95%CI 16.2-NE) in Arm B (CT). Median OS was not reached in patients with SUV≥2. 60-month OS rate was 41.6% (95%CI 10.4–71.1%) in Arm A, 42.0% (95%CI 14.0–68.2%) in Arm B and 59.6% (95%CI 48.6–69.0%) in patients with SUV≥2. In patients with SUV≥2, 60-months OS rate was 72.6% if treated with aromatase inhibitors versus 40.6% in case of fulvestrant or tamoxifen (p<0.005). Conclusions: The ET-FES trial demonstrated that ER+/HER2- MBC patients are a heterogeneous population, with different levels of endocrine responsiveness based on 18F-FES CT/PET SUV.