Résumé
Introduction: Post CDK4/6i second line endocrine therapy-based treatment options have recently expanded for patients with ER-positive/HER2-negative ABC, with new endocrine therapies (ngSERDs) and combination therapies (PI3KCA/AKTi, CDKi) being available or under investigation. Additionally, antibody-drug conjugates such as T-DXd (Destiny-Breast 06, ASCO 2024) have also demonstrated prolonged efficacy in the post-CDK4/6i setting and could become an attractive treatment option. Interestingly, while ER loss/downregulation is a universal mechanism of resistance to endocrine therapy, [18F]fluoroestradiol (FES) PET/CT enables non-invasive assessment of ER expression and heterogeneity in ABC lesions. This information may guide therapy selection in the post-CDK4/6i setting, potentially reducing the use of ineffective endocrine therapies in these patients. Methods: ESTROTIMP is an ongoing multicenter trial in France, prospectively enrolling 152 patients with progression of ER-positive/HER2-negative ABC on first-line endocrine therapy in combination with a CDK4/6 inhibitor. After standard of care [18F]fluorodeoxyglucose (FDG) PET/CT, all patients undergo an FES PET/CT scan. Treating physicians complete therapeutic management questionnaires before and after the FES PET/CT to evaluate the impact on therapeutic management. Nuclear medicine physicians complete reading forms for both FDG and FES PET/CT scans. Patients score pain and apprehension for both FES PET/CT and biopsy on a Visual Analogue Scale (VAS). Quality of life and second-line progression free survival (compared to a matched retrospective cohort) will be assessed after 12 months. An interim analysis of the first 30 assessable prospective patients has been conducted. Results: FES uptake in ABC lesions was classified as all lesions ER-positive (when compared with FDG PET/CT) in 19 of 30 patients (63.3%), mixed ER-positive/negative lesions in 7 (23.3%), and all lesions ER-negative in 4 patients (13.3%). A therapeutic management change based on incorporation of FES PET/CT results was implemented in 11 of 30 patients (36.7%; 99% confidence interval 16.0 - 61.6). Therapy selection was changed in 9 patients and diagnostic testing in 5, including 3 patients with changes in both. FES PET/CT helped confirm the initial management plan in 17 of 19 patients without changes in the management decision. Patients reported significantly lower pain and apprehension VAS scores for FES PET/CT compared to biopsy (Pain: Mean [SD], 1.00 [2.304] vs. 2.95 [3.197]; p=0.0051. Apprehension: Mean [SD], 2.47 [3.126] vs. 4.81 [3.636]; p=0.0111). Conclusions: FES PET/CT is a helpful tool to inform therapeutic management decisions in patients with progression of ER-positive/HER2-negative ABC on first-line therapy and procedurally showed lower pain and apprehension scores compared to biopsy.
Citation Format: Francois-Clement Bidard, Bidard, Romain-David Seban, Stephanie van de Ven, Sylvain Ladoire, Audrey Bellesoeur, Sandrine Parisse-Di Martino, Olivier Humbert, Thibaut Cassou-Mounat, Emmanuel Deshayes, Loic Djaileb, Khaldoun Kerrou, Eve Piekarski, Elise Deluche, Alexandre Cochet. [18F]fluoroestradiol (FES) PET/CT to guide 2nd line treatment decision in patients with ER-positive HER2-negative advanced breast cancer (ABC) progressing on 1st line aromatase inhibitor and CDK4/6 inhibitor: early results of the ESTROTIMP trial [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr PS11-02.