Stage 1 results from MDV3100-11: A 2-stage study of enzalutamide (ENZA), an androgen receptor (AR) inhibitor, in advanced AR+ triple-negative breast cancer (TNBC)

Abstract

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 castrationresistant 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 openlabel, 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. (Table Presented).