AR expression has been observed in 10-30% of patients with TNBC. AR+ TNBC cell lines demonstrated enhanced growth in response to androgen stimulation that is inhibited by enzalutamide (ENZA), a potent oral inhibitor of AR signaling. AR+ TNBC may represent a subtype driven by AR signaling that may respond to ENZA.


MDV3100-11 is an open-label, Simon 2-stage study designed to evaluate single agent ENZA (160 mg PO daily) in women with advanced AR+ TNBC (NCT01889238). Patients must have measurable or bone-only non-measurable disease. Baseline CNS imaging is required to exclude patients with CNS metastases. Patients with a seizure history are excluded. "AR+" for eligibility is defined as any nuclear AR expression by immunohistochemistry (IHC); TNBC is defined as estrogen receptor and progesterone receptor <1% by IHC and human epidermal growth factor receptor 2 IHC 0 or 1+ or non-amplified for IHC 2+. The primary endpoint is clinical benefit rate (CBR), defined as complete or partial response (CR or PR) or stable disease ≥16 weeks as assessed by the Investigator according to RECIST 1.1 based on the evaluable patient population. Additional endpoints include CBR at 24 weeks, response rates, safety, and tolerability. An evaluable patient is defined as having ≥10% AR staining and a postbaseline tumor assessment for response by RECIST 1.1. The study enrolls a total of 62 evaluable patients if the primary endpoint is achieved by ≥3 patients among the first 26 evaluable patients in Stage 1.


Preliminary results are available for a subset of the first 26 evaluable patients enrolled; 14 patients have discontinued study due to progressive disease at week 16 or earlier. Eight patients have achieved the primary endpoint; 4 additional active patients have not had their week 16 assessment but achieved stable disease or better at 8 weeks. The current CBR rate is therefore 31%, and could go as high as 46% if all 4 additional patients show at least stable disease or better at their week 16 assessment. Of the 8, 2 discontinued (1 each at weeks 21 and 37), 2 had objective responses (1 PR and 1 CR), and 6 have been on study for ≥24 weeks without disease progression. The toxicity profile of ENZA is so far consistent with other hormone therapies. Full safety and efficacy data on the first 26 evaluable patients enrolled in Stage 1 will be available for inclusion at the time of the late breaking abstract.


Currently, there is no targeted therapy approved for patients with TNBC. Cytotoxics remain the standard of care in this setting. Preliminary activity and tolerability observed with ENZA are encouraging and raise the possibility that some patients with TNBC may benefit from targeted inhibition of AR signaling, thereby avoiding or delaying cytotoxic regimens.

Placeholder abstract: This is a placeholder abstract; we are expecting results from the first subset of 26 evaluable patients to be ready by September 2014.

Citation Format: Tiffany A Traina, Joyce O'Shaughnessy, Rita Nanda, Lee Schwartzberg, Vandana Abramson, Javier Cortes, Amy Peterson, Iulia Cristina Tudor, Martha Blaney, Joyce L Steinberg, Catherine Kelly, Maureen Trudeau, Ahmad Awada, Eric Winer, Clifford Hudis, Peter Schmid, Denise A Yardley. Preliminary results from a phase 2 single-arm study of enzalutamide, an androgen receptor (AR) inhibitor, in advanced AR+ triple-negative breast cancer (TNBC) [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-19-09.