A phase 1b study evaluating the effect of elacestrant treatment on estrogen receptor availability and estradiol binding to the estrogen receptor in metastatic breast cancer lesions using 18F-FES PET/CT imaging
Abstract Background Elacestrant is an oral selective estrogen receptor (ER) degrader. This phase 1b open-label, non-randomized study (RAD1901-106) was initiated to determine the effect of elacestrant on the availability of ER in lesions from postmenopausal women with ER+ advanced breast cancer (ABC)...
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doaj-b93108018a2e49f1b6e045dbee2472a82021-04-02T12:39:06ZengBMCBreast Cancer Research1465-542X2020-09-0122111110.1186/s13058-020-01333-3A phase 1b study evaluating the effect of elacestrant treatment on estrogen receptor availability and estradiol binding to the estrogen receptor in metastatic breast cancer lesions using 18F-FES PET/CT imagingAgnes Jager0Elisabeth G. E. de Vries1C. Willemien Menke-van der Houven van Oordt2Patrick Neven3Clasina M. Venema4Andor W. J. M. Glaudemans5Yamei Wang6Rebecca G. Bagley7Maureen G. Conlan8Philippe Aftimos9Erasmus MC Cancer InstituteUniversity Medical Center Groningen, University of GroningenAmsterdam UMC location VUMC, Cancer Center AmsterdamUZ KU-LeuvenUniversity Medical Center Groningen, University of GroningenUniversity Medical Center Groningen, University of GroningenRadius Health, Inc.Radius Health, Inc.Radius Health, Inc.Clinical Trials Conduct Unit, Institut Jules Bordet – Université Libre de BruxellesAbstract Background Elacestrant is an oral selective estrogen receptor (ER) degrader. This phase 1b open-label, non-randomized study (RAD1901-106) was initiated to determine the effect of elacestrant on the availability of ER in lesions from postmenopausal women with ER+ advanced breast cancer (ABC) using 16α-18F-fluoro-17β-estradiol positron emission tomography with low-dose computed tomography (FES-PET/CT). Methods Eligible patients were postmenopausal women with ER+, HER2− ABC; tumor progression after ≥ 6 months of 1–3 lines of endocrine treatment for ABC; and measurable or evaluable disease. Two 8-patient cohorts were enrolled: one treated with 400 mg elacestrant once daily (QD) and one treated with 200 mg elacestrant QD with dose escalation to 400 mg QD after 14 days. Elacestrant was dosed continuously until progressive disease, toxicity, or withdrawal. FES-PET/CT was performed pre-dose at baseline and 4 h post-dose on day 14. The primary endpoint was the percentage difference in FES uptake in tumor lesions (maximum 20) after 14 days of treatment compared to baseline. Overall response was investigator-assessed by Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1. Results Patients (n = 16; median age, 53.5 years) had ABC with a median 2.5 prior lines of endocrine therapy. Median reduction in tumor FES uptake from baseline to day 14 was 89.1% (Q1, Q3: 75.1%, 94.1%) and was similar in both cohorts (89.1% [Q1, Q3: 67.4%, 94.2%], 200/400 mg and 88.7% [Q1, Q3: 79.5%, 94.1%], 400 mg). Residual ER availability (> 25% persistence in FES uptake) on day 14 was observed in 3 patients receiving 200/400 mg (3/78, 37.5%) and 1 patient receiving 400 mg (1/8, 12.5%). The overall response rate (ORR) was 11.1% (1 partial response), and clinical benefit rate (CBR) was 30.8%. Median percentage change in FES uptake did not correlate with ORR or CBR. Adverse events occurring in > 20% of the patients were nausea (68.8%), fatigue (50.0%), dyspepsia (43.8%), vomiting (37.5%), and decreased appetite, dysphagia, and hot flush (31.3% each). Most events were grade 2 in severity. Conclusion Elacestrant 200 mg and 400 mg QD greatly reduced ER availability measured by FES-PET/CT. In a heavily pretreated population, elacestrant was associated with antitumor activity. Trial registration ClinicalTrials.gov, NCT02650817 . Registered on 08 January 2016http://link.springer.com/article/10.1186/s13058-020-01333-3Advanced breast cancerElacestrantEndocrine therapyEstrogen receptor16α-18F-fluoro-17β-estradiol (FES)Hormonal therapy |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Agnes Jager Elisabeth G. E. de Vries C. Willemien Menke-van der Houven van Oordt Patrick Neven Clasina M. Venema Andor W. J. M. Glaudemans Yamei Wang Rebecca G. Bagley Maureen G. Conlan Philippe Aftimos |
spellingShingle |
Agnes Jager Elisabeth G. E. de Vries C. Willemien Menke-van der Houven van Oordt Patrick Neven Clasina M. Venema Andor W. J. M. Glaudemans Yamei Wang Rebecca G. Bagley Maureen G. Conlan Philippe Aftimos A phase 1b study evaluating the effect of elacestrant treatment on estrogen receptor availability and estradiol binding to the estrogen receptor in metastatic breast cancer lesions using 18F-FES PET/CT imaging Breast Cancer Research Advanced breast cancer Elacestrant Endocrine therapy Estrogen receptor 16α-18F-fluoro-17β-estradiol (FES) Hormonal therapy |
author_facet |
Agnes Jager Elisabeth G. E. de Vries C. Willemien Menke-van der Houven van Oordt Patrick Neven Clasina M. Venema Andor W. J. M. Glaudemans Yamei Wang Rebecca G. Bagley Maureen G. Conlan Philippe Aftimos |
author_sort |
Agnes Jager |
title |
A phase 1b study evaluating the effect of elacestrant treatment on estrogen receptor availability and estradiol binding to the estrogen receptor in metastatic breast cancer lesions using 18F-FES PET/CT imaging |
title_short |
A phase 1b study evaluating the effect of elacestrant treatment on estrogen receptor availability and estradiol binding to the estrogen receptor in metastatic breast cancer lesions using 18F-FES PET/CT imaging |
title_full |
A phase 1b study evaluating the effect of elacestrant treatment on estrogen receptor availability and estradiol binding to the estrogen receptor in metastatic breast cancer lesions using 18F-FES PET/CT imaging |
title_fullStr |
A phase 1b study evaluating the effect of elacestrant treatment on estrogen receptor availability and estradiol binding to the estrogen receptor in metastatic breast cancer lesions using 18F-FES PET/CT imaging |
title_full_unstemmed |
A phase 1b study evaluating the effect of elacestrant treatment on estrogen receptor availability and estradiol binding to the estrogen receptor in metastatic breast cancer lesions using 18F-FES PET/CT imaging |
title_sort |
phase 1b study evaluating the effect of elacestrant treatment on estrogen receptor availability and estradiol binding to the estrogen receptor in metastatic breast cancer lesions using 18f-fes pet/ct imaging |
publisher |
BMC |
series |
Breast Cancer Research |
issn |
1465-542X |
publishDate |
2020-09-01 |
description |
Abstract Background Elacestrant is an oral selective estrogen receptor (ER) degrader. This phase 1b open-label, non-randomized study (RAD1901-106) was initiated to determine the effect of elacestrant on the availability of ER in lesions from postmenopausal women with ER+ advanced breast cancer (ABC) using 16α-18F-fluoro-17β-estradiol positron emission tomography with low-dose computed tomography (FES-PET/CT). Methods Eligible patients were postmenopausal women with ER+, HER2− ABC; tumor progression after ≥ 6 months of 1–3 lines of endocrine treatment for ABC; and measurable or evaluable disease. Two 8-patient cohorts were enrolled: one treated with 400 mg elacestrant once daily (QD) and one treated with 200 mg elacestrant QD with dose escalation to 400 mg QD after 14 days. Elacestrant was dosed continuously until progressive disease, toxicity, or withdrawal. FES-PET/CT was performed pre-dose at baseline and 4 h post-dose on day 14. The primary endpoint was the percentage difference in FES uptake in tumor lesions (maximum 20) after 14 days of treatment compared to baseline. Overall response was investigator-assessed by Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1. Results Patients (n = 16; median age, 53.5 years) had ABC with a median 2.5 prior lines of endocrine therapy. Median reduction in tumor FES uptake from baseline to day 14 was 89.1% (Q1, Q3: 75.1%, 94.1%) and was similar in both cohorts (89.1% [Q1, Q3: 67.4%, 94.2%], 200/400 mg and 88.7% [Q1, Q3: 79.5%, 94.1%], 400 mg). Residual ER availability (> 25% persistence in FES uptake) on day 14 was observed in 3 patients receiving 200/400 mg (3/78, 37.5%) and 1 patient receiving 400 mg (1/8, 12.5%). The overall response rate (ORR) was 11.1% (1 partial response), and clinical benefit rate (CBR) was 30.8%. Median percentage change in FES uptake did not correlate with ORR or CBR. Adverse events occurring in > 20% of the patients were nausea (68.8%), fatigue (50.0%), dyspepsia (43.8%), vomiting (37.5%), and decreased appetite, dysphagia, and hot flush (31.3% each). Most events were grade 2 in severity. Conclusion Elacestrant 200 mg and 400 mg QD greatly reduced ER availability measured by FES-PET/CT. In a heavily pretreated population, elacestrant was associated with antitumor activity. Trial registration ClinicalTrials.gov, NCT02650817 . Registered on 08 January 2016 |
topic |
Advanced breast cancer Elacestrant Endocrine therapy Estrogen receptor 16α-18F-fluoro-17β-estradiol (FES) Hormonal therapy |
url |
http://link.springer.com/article/10.1186/s13058-020-01333-3 |
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