Abstract P1-10-04: Elacestrant, a novel oral selective estrogen receptor degrader (SERD), decreases tumoral 18F-FES uptake in a phase 1 study of ER+, HER2 -, advanced breast cancer patients
Authors: de Vries EGE , Venema CM , Glaudemans AWJM , Jager A , Menke-van der Houven van Oordt CW , Neven P , Jiang H , Wang D , O'Neill A , Patki A , Aftimos P 
Published: February 2018

Abstract
Background: The estrogen receptor (ER) expressed in approximately 70% of breast cancers, can be mapped using 16α-[18F]Fluoro-17β-estradiol (FES)-PET, a non-invasive molecular whole body imaging tool capable of assessing ER target engagement by endocrine therapy. Elacestrant (RAD1901) is a novel, non-steroidal oral SERD that has demonstrated single-agent activity in heavily pre-treated patients with ER+ advanced breast cancer (Bardia et al., J Clin Oncol 35, 2017: suppl; abstr 1014).
The primary objective of this study was the visualization and quantification of residual ER-binding with FES-PET after treatment with elacestrant.
Methods: In the RAD1901-106 phase 1 study (NCT02650817), patients with advanced ER+/HER2 - breast cancer were treated with elacestrant at two dose levels (200 mg or 400 mg qd orally) for the first 14 days. Tumoral FES uptake was measured at baseline and day 14. After FES-PET scan at day 14, all patients received elacestrant 400 mg qd until disease progression or discontinuation due to another cause. Key inclusion criteria included postmenopausal women with advanced ER+/HER2- breast cancer, who have progressed after ≥6 months of at least 1 line of endocrine treatment in the metastatic setting, with measurable disease according to RECIST criteria v1.1 or clinically evaluable disease. The PET scan was performed 60 min after intravenous injection of 200 MBq FES. Maximum standardized uptake values (SUVmax) were calculated and corrected for background activity. FES positive lesions had a SUVmax &gt;1.5. FES response was defined as a ≥ 75% median decrease of SUVmax between the two scans. ESR1 mutation status was determined from circulating tumor DNA collected at multiple time points.
Results: Twenty-four patients were screened and 16 patients were enrolled (8 at each dose level). Median lines of prior therapy were 3, with 6 (38%) patients having previously received fulvestrant and 8 (50%) patients harboring at least 1 ESR1 mutation at baseline. Elacestrant demonstrated a median of 88% (range 59-97.1%) reduction in tumorFES uptake following 14 days of treatment. Eleven out of 16 patients had &gt;75% reduction in FES uptake at day 14. At the data cutoff date of 2 May 2017, median treatment duration was 8.1 weeks and 8 (50%) patients remained on study. Elacestrant was generally well-tolerated, with the most common treatment-related adverse events (CTCAE v4.03) being low grade nausea gr1 = 50%; gr2 =19%; gr3/4 = 0%), dyspepsia (gr1= 25%; gr2 = 19%; gr3/4 = 0%) and dysphagia (gr1 = 19%; gr2 =12%; gr3/4 = 0%). Updated analyses with mature data on correlation of FES uptake reduction and tumor response, treatment duration, safety and ESR1 mutation will be presented.
Conclusions: Elacestrant significantly reduced FES uptake at both 200 mg and 400 mg doses after 14 days of treatment in heavily pre-treated patients with advanced ER+/HER2- breast cancer, including those harboring ESR1 mutations.
Citation Format: de Vries EGE, Venema CM, Glaudemans AWJM, Jager A, Menke-van der Houven van Oordt CW, Neven P, Jiang H, Wang D, O'Neill A, Patki A, Aftimos P. Elacestrant, a novel oral selective estrogen receptor degrader (SERD), decreases tumoral 18F-FES uptake in a phase 1 study of ER+, HER2 -, advanced breast cancer patients [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-10-04.