Abstract P4-22-23: Phase II trial of selinexor for metastatic triple negative breast cancer
Authors: Han HS , Ismail-Khan R , Carney D , Extermann M , Hogue D , Soliman H , Loftus L , Lee JK , Sullivan D 
Published: May 2019

Abstract
Background: XPO1 (also known as CRM1) is the exclusive nuclear exporter of multiple tumor suppressor proteins (TSP) including p53, p21, BRCA1/2, pRB, FOXO. XPO1 inhibition forces nuclear accumulation of TSPs, thus inducing apoptosis in cancer cells. Selective Inhibitors of Nuclear Export (SINE) compounds are novel, small molecule, slowly reversible inhibitors of XPO1. SINE compounds showed potent cytotoxicity in the majority of TNBC cell lines in vitro and xenografts.
Methods: Eligible patients had measurable metastatic TNBC, received at least one prior line of chemotherapy in the setting of metastatic disease (including anthracycline and taxane), and had an ECOG PS 0-1. Selinexor was given at 60 mg orally twice weekly (day 1& 3 of each week), three of each four-week cycle. The primary objective of this study was to determine the clinical benefit rate (CBR, defined as complete response + partial response + stable disease (SD) ≥12 weeks) from Selinexor in patients with TNBC. This study used a Simon two-stage design (null hypothesis CBR 5%, alternate hypothesis CBR 20%)
Results: Ten patients with a median age of 60 years (range 44-71) were enrolled between 7/2015 and 1/2016. The median number of prior chemotherapy lines was 2 (range 1-5). A planned interim analysis for the first stage per protocol was performed. Three patients had SD and 7 had progressive disease. The median duration of SD was 84 days (range 17-130 days) and all patients experienced progressive disease with a median PFS of 38 days (range 17-130 days). Based on these results, the error probability of observing no response among the first 10 patients is 0.107 under the alternative hypothesis, i.e., P of response =20%, using the Exact binomial test. This false negative error rate is under the planned type II error 0.20, which is consistent with the predefined stopping rule of the study: the study would be halted if no patient achieved objective response (complete or partial response) in the first 10 eligible patients (stage I).
The most frequent grade 1 and 2 observed adverse events that were possibly related to Selinexor were nausea 30% (all grade 1), vomiting 50% (40% grade 1), constipation 50% (40% grade 1, 10% grade 2), diarrhea 20%, anorexia 30%, thrombocytopenia 30%, blurred vision 30%. No grade 4 toxicity was noted. Grade 3 toxicity included reversible encephalopathy (10%), irritability (10%), and thrombocytopenia (10%).
Conclusion: Selinexor was well tolerated in patients with advanced TNBC but did not result in objective responses in this patient population. Further combination studies can be explored.
Citation Format: Han HS, Ismail-Khan R, Carney D, Extermann M, Hogue D, Soliman H, Loftus L, Lee JK, Sullivan D. Phase II trial of selinexor for metastatic triple negative breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-22-23.