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 18 F-FES PET/CT imaging.

Autor: Jager A; Erasmus MC Cancer Institute, Post Office Box 2040, 3000 CA, Rotterdam, Netherlands., de Vries EGE; University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ, Groningen, Netherlands., der Houven van Oordt CWM; Amsterdam UMC location VUMC, Cancer Center Amsterdam, De Boelelaan 1118, 1081 HV, Amsterdam, Netherlands., Neven P; UZ KU-Leuven, Herestraat 49, 3000, Leuven, Belgium., Venema CM; University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ, Groningen, Netherlands., Glaudemans AWJM; University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ, Groningen, Netherlands., Wang Y; Radius Health, Inc., 950 Winter Street, Waltham, MA, 02451, USA., Bagley RG; Radius Health, Inc., 950 Winter Street, Waltham, MA, 02451, USA., Conlan MG; Radius Health, Inc., 950 Winter Street, Waltham, MA, 02451, USA. mconlan@radiuspharm.com., Aftimos P; Clinical Trials Conduct Unit, Institut Jules Bordet - Université Libre de Bruxelles, Rue Héger-Bordet 1, 1000, Brussels, Belgium.
Jazyk: angličtina
Zdroj: Breast cancer research : BCR [Breast Cancer Res] 2020 Sep 11; Vol. 22 (1), pp. 97. Date of Electronic Publication: 2020 Sep 11.
DOI: 10.1186/s13058-020-01333-3
Abstrakt: 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- 18 F-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.
Databáze: MEDLINE
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