Results from a phase 2 study of enzalutamide (ENZA), an androgen receptor (AR) inhibitor, in advanced AR+ triple-negative breast cancer (TNBC).

Breast Cancer—Triple-Negative/Cytotoxics/Local Therapy
Session Type and Session Title: 
Oral Abstract Session, Breast Cancer—Triple-Negative/Cytotoxics/Local Therapy
Abstract Number: 


J Clin Oncol 33, 2015 (suppl; abstr 1003)
Tiffany A. Traina, Kathy Miller, Denise A. Yardley, Joyce O'Shaughnessy, Javier Cortes, Ahmad Awada, Catherine Margaret Kelly, Maureen E. Trudeau, Peter Schmid, Luca Gianni, Laura García-Estevez, Rita Nanda, Foluso Olabisi Ademuyiwa, Stephen Chan, Joyce Leta Steinberg, Martha Elizabeth Blaney, Iulia Cristina Tudor, Hirdesh Uppal, Amy C. Peterson, Clifford A. Hudis; Memorial Sloan Kettering Cancer Center, New York, NY; Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN; Sarah Cannon Research Institute, Tennessee Oncology, PLLC, Nashville, TN; Baylor Sammons Cancer Ctr US Onc, Dallas, TX; Vall D'Hebron University Hospital, Barcelona, Spain; Jules Bordet Institute, Bruxelles, Belgium; Mater Misericordiae University Hospital, Dublin, Ireland; Sunnybrook Health Sciences Centre, Toronto, ON, Canada; University of Sussex, London, United Kingdom; San Raffaele Hospital, Milano, Italy; Centro Integral Oncológico Clara Campal, Madrid, Spain; University of Chicago, Chicago, IL; Washington Univ School of Medicine, St. Louis, MO; Nottingham University Hospital City Campus, Nottingham, United Kingdom; Astellas Pharma US Inc, Northbrook, IL; Medivation, San Francisco, CA; Medivation, Inc., San Francisco, CA; Medivation Inc, San Francisco, CA

Abstract Disclosures


Background: The AR may be a therapeutic target for pts with androgen-driven TNBC. ENZA, a potent AR inhibitor, is approved in men with metastatic castration-resistant prostate cancer (mCRPC) and improves median PFS compared to bicalutamide in men with mCRPC (15.7 vs 5.8 mos; HR 0.44; p<0.0001). Methods: MDV3100-11 was an open-label, Simon 2-stage study evaluating single agent ENZA in advanced AR+ TNBC (AR >0% by IHC; NCT01889238). Pts could be prescreened for AR, and have non-measurable bone disease and unlimited prior regimens; CNS metastases or seizure history were exclusionary. The primary endpoint was clinical benefit (CR, PR or SD) at 16 wks (CBR16) in ‘Evaluable’ pts defined as having both AR IHC ≥10% and a response assessment. CBR24, PFS, response rate, and safety were assessed. An androgen-driven gene signature (Dx) was created from gene profiling and outcomes were assessed accordingly. Stage 2 enrolled if CBR16 was ≥3 of 26 Evaluable pts; H0 was rejected if CBR16 was ≥9 in 62 yielding 85% power at 5% significance to test against a 1-sided alternative (CBR16 ≥20%). Results: As of 16 JAN 2015, 404 samples were tested for AR IHC: 79% had AR >0%; 55% had AR ≥10%. 118 pts were treated with ENZA; 43 pts were not Evaluable (29 AR <10%; 14 AR ≥10% but no response assessment). Key outcomes in the defined populations are below as shown in the Table. Over 50% received ENZA as 1st or 2nd line; mPFS in these pts was 32 wks in Dx+ and 9 wks in Dx-. Two CRs and 5 PRs have been observed. Related AEs in ≥10% of 118 pts were fatigue (34%), nausea (25%), decreased appetite (13%), diarrhea and hot flush (10%). Fatigue (5%) was the only AE ≥ Grade 3 in ≥5%. Conclusions: This is the largest study of an AR inhibitor in TNBC. IHC results suggest AR prevalence is higher than previously reported. 47% of pts had an androgen-related gene signature (Dx+) and clinical outcomes appeared superior in this group. AEs from ENZA were consistent with its known profile. ENZA may represent a novel therapeutic option in pts with TNBC who would otherwise receive cytotoxic chemotherapy. Clinical trial information: NCT01889238

CBR16, % (95% CI)35 (24-46)39 (27-53)11 (5-21)
CBR24, % (95% CI)29 (20-41)36 (24-49)7 (2-16)
mPFS, wks (95% CI)14 (8-19)16 (10-32)8 (7-13)