In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. 560-560
Kurzfassung:
560 Background: Patients with TNBC breast cancer have inferior treatment outcomes compared to other breast cancer subtypes and targeted therapies are lacking. S-equol is a novel oral Estrogen Receptor (ER) Beta agonist with preclinical data showing suppression of TNBC cellular proliferation. We therefore conducted an early phase window of opportunity trial to evaluate the impact of S-equol on Ki-67 change in patients with TNBC. Methods: This neoadjuvant window trial enrolled 39 patients with confirmed TNBC on diagnostic core needle biopsy. Cohort A (20 patients) received a daily dose of 50 mg daily and Cohort B (19 patients) received a higher dose of 150 mg daily. Paired biopsies were evaluable for 36 patients. Both cohorts were treated for a duration of 10-21 days. Primary outcome was change from pre- to post-treatment Ki-67 evaluated by paired t-test. All tests were 2-sided with a significance level of 0.05. Statistics were conducted within an accountable data analysis process in R (ADAPR). Secondary outcomes included toxicity and correlative biomarkers. Results: The mean (SD) pre-treatment was 68% (21.99) and post-treatment 59% (20.62). The average decrease in Ki-67 was 8% (P = 0.00206, 95% CI -13.46 to -3.26). A Ki-67 decrease of at least 20% from baseline was observed in 28% of the patients. S-equol was well tolerated with the most common toxicities being nausea, constipation, diarrhea, and headache. All toxicities were grade one. Treatment compliance was greater than 95%. Planned correlative studies included RNA-seq. A total of 161 genes are differentially expressed with fold change 〉 = 2 and p value 〈 0.05. The top genes of the differential expression list include BMP5, S100A7, FABP7, SCGB2A2, CH507-338C24.1, and DUSP1. Gene Set Enrichment Analysis (GSEA) indicates that top enriched gene modules are related to interferon function and immune response, most of which are downregulated in the post-treatment group. Conclusions: S-equol is a novel well tolerated oral ER-Beta agonist with inhibition of proliferation in patients with TNBC as measured by a decrease in Ki-67. RNA-seq data supports potential immune activation during this short period of drug exposure. Future studies aim to evaluate S-equol as an immune activating agent for combination with immunotherapies such as checkpoint inhibitors in TNBC. Clinical trial information: NCT02352025 .
Materialart:
Online-Ressource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2020.38.15_suppl.560
Sprache:
Englisch
Verlag:
American Society of Clinical Oncology (ASCO)
Publikationsdatum:
2020
ZDB Id:
2005181-5
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