ABSTRACT
Background: Estrogen receptors (ER) are predictive of endocrine responsiveness. However, 30% of ER+ BC patients will relapse despite adjuvant ET and 10 to 20% of metastatic lesions loose the expression of ER. The early identification of endocrine resistant patients may help to improve treatment strategies, especially in the light of innovative drugs recently approved. In the ET-FES trial we evaluated 18F-FES CT/PET as a prediction tool for endocrine responsiveness in ER+ MBC. The ET-FES study was funded by the ERANET-Transcan project. Methods: MBC patients with ER+/HER2- disease, were eligible for the ET/FES study. All patients underwent a baseline [18]F-FES PET/CT in addition to conventional procedures. Patients were classified as endocrine sensitive if overall Standardized Uptake Value (SUV) ≥ 2 and received ET;patients with SUV <2 were randomized to receive ET or chemotherapy (CT). The prognostic role of [18]F-FES PET/CT was assessed for PFS and OS by univariate and multivariate analyses. The primary endpoint was disease progression rate (DPR) at 6 months. Results: From April 2015 to October 2020 146 patients, from 7 EU centers were enrolled: of them, 115 with a mean SUV >2 received ET and 30 with SUV <2 were included in the randomized study. Median follow up was 18.4 months (range 8.0 to 38.3 months) in endocrine sensitive patients (SUV > 2) versus 10.1 months (range 8.0 to 36.8) in patients with SUV <2. Overall, at the time of this analysis 67 patients (45.9%) had disease progression and 37 (25.3%) died. DPR at 6 months was 57% in patients with SUV >2 vs 50% in SUV <2 randomized to ET and 57% in case of CT. DPR at 12 months was 35% vs 17% and 14%, respectively. Median PFS was 7.3 months (IQR 3.8 – 17.3) vs 5.2 (IQR 3.1 – 9.4) vs 7.7 months (IQR 3.0 – 14.0), respectively. OS rate at 12 months was 31% versus 17% versus 14%. Conclusions: The ET-FES clinical trial was prematurely interrupted, due to COVID-19 pandemic. The discriminating ability of this assay was high, leading to a personalized endocrine approach;a considerable proportion of patients with a mean SUV >2 is still on ET. Clinical trial identification: EudraCT 2013-000287-29. Legal entity responsible for the study: Alessandra Gennari - Università del Piemonte Orientale. Funding: AIRC. Disclosure: All authors have declared no conflicts of interest.