期刊
CLINICAL CANCER RESEARCH
卷 29, 期 11, 页码 2075-2084出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-22-2720
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The purpose of this study was to investigate the use of [18F]-fluorodeoxyglucose ([18F]FDG) and [18F]-fluoro-17(3-estradiol ([18F]FES) PET/CT imaging in patients with metastatic ER-positive breast cancer undergoing treatment with rintodestrant. The study found that absence of ER expression on [18F]FES PET is a predictor for no response to rintodestrant. [18F]FES uptake during treatment and at time of progression is useful to monitor the effect of therapy and continued mode of action of SERDs.
Purpose: PET with 16a-[18F]-fluoro-17(3-estradiol ([18F]FES) allows assessment of whole body estrogen receptor (ER) expression. The aim of this study was to investigate [18F]-fluorodeoxyglucose ([18F]FDG) and [18F]FES PET/CT imaging for response prediction and monitoring of drug activity in patients with metastatic ER-positive breast cancer undergoing treatment with the selective estrogen receptor downregulator (SERD) rintodestrant.Experimental Design: In this trial (NCT03455270), PET/CT imaging was performed at baseline ([18F]FDG and [18F]FES), during treatment and at time of progression (only [18F]FES). Visual, quantitative, and mutational analysis was performed to derive a heterogeneity score (HS) and assess tracer uptake in lesions, in relation to the mutation profile. The primary outcome was pro-gression-free survival (PFS).Results: The HS and PFS in the entire group did not correlate (n = 16, Spearman's rho, P = 0.06), but patients with a low HS (< 25.0%, n = 4) had a PFS of > 5 months whereas patients with no [18F]FES uptake (HS 100.0%, n = 3) had a PFS of < 2 months. [18F]FES uptake was not affected by estrogen receptor 1 (ESR1) mutations. On-treatment [18F]FES PET/CT scans showed no [18F]FES uptake in any of the baseline [18F]FES-positive lesions. At progression, [18F]FES uptake remained blocked in patients scanned <= 1-2 half-lives of rintodestrant whereas it restored in patients scanned >= 5 days after end of treatment.Conclusions: Absence of ER expression on [18F]FES PET is a predictor for no response to rintodestrant. [18F]FES uptake during treatment and at time of progression is useful to monitor the (reversible) effect of therapy and continued mode of action of SERDs.
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