Clinical utility of [ ¹⁸ F]fluoroestradiol (FES) PET/CT to guide second-line treatment decision in patients with ER-positive HER2-negative metastatic breast cancer progressing on first-line endocrine therapy.

1059 Background: Second line treatment options for patients with ER+/HER2- metastatic breast cancer (MBC) after progression on 1 st line endocrine therapy (ET) continue to expand with novel endocrine agents (oral SERDs) and combination therapies (PIK3CA/AKTi, CDKi). However, short median PFS reported in clinical trials show that many patients do not benefit from 2 nd line ET. Identifying endocrine-resistant MBC at time of progression on 1 st line ET can help place patients on potentially more effective non-ET options (e.g., chemotherapy / antibody-drug conjugates). FES PET/CT has been approved for clinical use in the U.S. and allows whole-body evaluation of ER expression in MBC. Difference in FES uptake across lesions may reflect ER loss/downregulation, a mechanism of endocrine resistance. Goal of this clinical trial was to evaluate the impact of FES PET/CT results on 2 nd line therapeutic management decisions. Methods: In this multicenter trial in the U.S. [NCT05068726], patients with progression of ER+/HER2- MBC on 1 st line ET were prospectively enrolled to undergo FES PET/CT in addition to standard of care (SOC) imaging (CT + bone scan / FDG PET/CT). Treating oncologists completed questionnaires before and after FES PET/CT, detailing therapeutic management plans plus their confidence in the plans. FES PET/CT scans were compared with SOC imaging to assess FES uptake in MBC lesions. An FES uptake score (number of FES-positive lesions divided by total number of lesions per patient) was calculated to evaluate ER expression heterogeneity by central blinded image evaluation. Results: 45 patients underwent FES PET/CT. FES PET/CT results led to a change in therapeutic management in 17/45 patients (37.8%; 95% CI 23.8% - 53.5%). Revised management plan was ET in 5/17 and non-ET in 12/17 patients. FES uptake score was 1 (all lesions FES-positive) in 14/45 patients and < 1 (with FES-negative lesions, indicating ER expression heterogeneity) in 31/45 patients. Of 14 patients with FES uptake score of 1, 11 received 2 nd line ET. Of 31 patients with FES uptake score < 1, 15 were treated with ET and 16 with non-ET, based on guidelines suggesting that an FES-negative lesion is predictive of lack of endocrine response. FES PET/CT results led to 25/45 patients avoiding additional tests (20 biopsies, 5 scans) and 7/45 patients receiving further testing (4 biopsies, 1 scan, 2 other). Treating oncologist’s confidence in 2 nd line treatment decision (measured in n = 45 on 10-point scale with 10 being fully confident) increased on average with 2 points from 6.6 (SD = 1.7) pre-FES PET/CT to 8.6 (SD = 1.8) post-FES PET/CT. Conclusions: FES PET/CT is a clinically useful tool in the post-first line ER+/HER2- MBC setting. FES PET/CT results led to a change in management in 37.8% of patients and increased oncologist’s confidence in 2 nd line treatment decision. Clinical trial information: NCT05068726 .