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

1003 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. Evaluable n=75 Dx+ n=56 Dx- n=62 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)