TY - JOUR
T1 - [18F]FDG and [18F]FES PET/CT Imaging as a Biomarker for Therapy Effect in Patients with Metastatic ER+ Breast Cancer Undergoing Treatment with Rintodestrant
AU - Iqbal, Ramsha
AU - Yaqub, Maqsood
AU - Bektas, Husseyin O
AU - Oprea-Lager, Daniela E
AU - de Vries, Elisabeth G E
AU - Glaudemans, Andor W J M
AU - Aftimos, Philippe
AU - Gebhart, Géraldine
AU - Beelen, Andrew P
AU - Schuit, Robert C
AU - Windhorst, Albert D
AU - Boellaard, Ronald
AU - Menke-van der Houven van Oordt, C Willemien
PY - 2023/6/1
Y1 - 2023/6/1
N2 - PURPOSE: Positron emission tomography (PET) with 16α-[18F]-fluoro-17β-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+ breast cancer undergoing treatment with the selective estrogen receptor downregulator (SERD) rintodestrant.PATIENTS AND METHODS: 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 progression-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 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.CONCLUSION: 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.
AB - PURPOSE: Positron emission tomography (PET) with 16α-[18F]-fluoro-17β-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+ breast cancer undergoing treatment with the selective estrogen receptor downregulator (SERD) rintodestrant.PATIENTS AND METHODS: 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 progression-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 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.CONCLUSION: 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.
U2 - 10.1158/1078-0432.CCR-22-2720
DO - 10.1158/1078-0432.CCR-22-2720
M3 - Article
C2 - 36735488
SN - 1078-0432
VL - 29
SP - 2075
EP - 2084
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 11
ER -