TY - JOUR
T1 - [18F]FDG and [18F]FES PET/CT Imaging as a Biomarker for Therapy Effect in Patients with Metastatic ERþ 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
AU - Bektas, Huseyyin O.
N1 - Funding Information: E.G.E de Vries reports other support from NSABP, Daiichi Sankyo, and Crescendo Biologics and grants from Amgen, Genentech, Roche, CytomX, G1 Therapeutics, Bayer, Synthon, Servier, Regeneron, Crescendo Biologics, GE Healthcare, and Astra-Zeneca outside the submitted work as well as and nonfinancial interests, including nonrenumerated activities and public positions: member of the ESMO-MCBS working party, chair of the ESMO cancer medicines working group, cochair of the RECIST committee, and member of the expert panel for selection of the WHO Essential Medicines List. P. Aftimos reports personal fees from G1 Therapeutics during the conduct of the study as well as personal fees from Boehringer Ingelheim, Macrogenics, Amgen, Roche, Novartis, Amcure, Servier, Deloitte, Synthon, and Gilead and other support from Daiichi Sankyo outside the submitted work. A.P. Beelen reports other support from G1 Therapeutics, Inc. outside the submitted work. A.D. Windhorst reports serving as editor-in-chief of Nuclear Medicine & Biology, a publication of Elsevier. C.W. Menke-van der Houven van Oordt reports grants from G1 Therapeutics during the conduct of the study as well as grants from Pfizer and other support from Radius outside the submitted work. No disclosures were reported by the other authors. Publisher Copyright: © 2023 American Association for Cancer Research.
PY - 2023/6/1
Y1 - 2023/6/1
N2 - Purpose: PET with 16a-[ 18F]-fluoro-17b-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 progression-free survival (PFS). Results: The HS and PFS in the entire group did not correlate (n ¼ 16, Spearman's rho, P ¼ 0.06), but patients with a low HS (< 25.0%, n ¼ 4) had a PFS of > 5 months whereas patients with no [ 18F]FES uptake (HS 100.0%, n ¼ 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.
AB - Purpose: PET with 16a-[ 18F]-fluoro-17b-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 progression-free survival (PFS). Results: The HS and PFS in the entire group did not correlate (n ¼ 16, Spearman's rho, P ¼ 0.06), but patients with a low HS (< 25.0%, n ¼ 4) had a PFS of > 5 months whereas patients with no [ 18F]FES uptake (HS 100.0%, n ¼ 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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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 : an official journal of the American Association for Cancer Research
JF - Clinical cancer research : an official journal of the American Association for Cancer Research
IS - 11
ER -