13P - Stage 1 results from MDV3100-11: A 2-stage study of enzalutamide (ENZA), an androgen receptor (AR) inhibitor, in advanced AR+ triple-negative breast...

Date 07 May 2015
Event IMPAKT 2015
Session Welcome reception and Poster Walk
Topics Anti-Cancer Agents & Biologic Therapy
Breast Cancer, Metastatic
Presenter Javier Cortes Castan
Citation Annals of Oncology (2015) 26 (suppl_3): 6-9. 10.1093/annonc/mdv115
Authors J. Cortes Castan1, P. Schmid2, A. Awada3, H. Uppal4, I.C. Tudor4, M.E. Blaney4, J.L. Steinberg5, D.A. Yardley6, C. Hudis7, T.A. Traina7
  • 1Breast Cancer Services, Vall d`Hebron University Hospital Institut d'Oncologia, 08035 - Barcelona/ES
  • 2Medical Oncology, Barts Cancer Institute-Queen Mary University of London, EC1M 6BQ - London/UK
  • 3Medical Oncology, Institute Jules Bordet, 1000 - Brussels/BE
  • 4Oncology, Medivation, San Francisco/US
  • 5Oncology, Astellas Pharma Global Development, Northbrook/US
  • 6Oncology, Sarah Cannon Research Institute, Nashville/US
  • 7Breast Medicine Services, Memorial Sloan-Kettering Cancer Center, New York/US



Background: AR expression occurs in a subset of TNBC and may identify patients (pts) who benefit from AR inhibition. ENZA, a potent oral AR inhibitor, improves OS in men with metastatic castration-resistant prostate cancer and is being evaluated in pts with advanced AR+ TNBC.

Methods: MDV3100-11 is an open-label, Simon 2-stage study evaluating ENZA in pts with AR expressing (>0% by IHC) TNBC; AR prescreening was allowed (NCT01889238). Bone-only disease was permitted with no limit on prior therapies. Pts with CNS metastases or seizure history were excluded. The primary endpoint is clinical benefit rate (CBR) at 16 wks (CBR16) in ‘evaluable’ pts, defined as having both AR IHC ≥10% (centrally) and a response assessment. CBR16 is complete or partial response (CR or PR) or stable disease ≥16 wks per RECIST 1.1. Secondary endpoints are CBR24, overall response rates and safety. Stage 2 enrolled if CBR16 was ≥3 of 26 ‘evaluable’ pts in Stage 1; the null hypothesis is rejected if CBR16 is ≥9 in 62 ‘evaluable’ pts.

Results: Over 400 tissue samples were received; 79% had some AR expression and 55% had AR ≥10%. Among the 42 pts enrolled into Stage 1, 16 pts were not ‘evaluable’ (10 had AR <10%; 6 had AR ≥10% but no response assessment). Of the 26 ‘evaluable’ pts, 77% had measurable disease, 62% had visceral involvement, 69% had ≥3 metastatic sites, and 35% received ≥3 prior regimens. CBR16 was 42% (11/26) and CBR24 was 35% (9/26), with 1 PR and 1 CR. Related adverse events (AEs) in ≥15% of all 42 pts were fatigue (36%), nausea (33%), diarrhea (21%) and decreased appetite (19%). Fatigue (7%) was the only AE ≥ Grade 3 in ≥5%. Go to Stage 2 criteria were met; enrollment is now complete at 118. As of Nov 2014, 27 pts reached CBR16 (including 4 PRs and 2 CRs); data continue to mature.

Conclusions: The 42% CBR16 observed in Stage 1 was sufficiently high to reject the null hypothesis for the whole study and a majority of pts with CBR16 also had CBR24. AEs were generally mild and consistent with other ENZA studies. These results suggest that ENZA may provide meaningful benefit to pts with metastatic AR+ TNBC. Genomic analyses on tumor tissues are underway and may better identify TNBC pts most likely to benefit from ENZA.

Clinical trial identification: NCT01889238

Disclosure: J. Cortes Castan: Consultant/Advisor: Celgene, Roche Honoraria: Novartis, Celgene, Roche, Eisai.

A. Awada: Board Membership: Nektar, Roche, Bayer.

H. Uppal, I.C. Tudor and M.E. Blaney: Employee: Medivation, Inc.

J.L. Steinberg: Employee: Astellas Pharma.

T.A. Traina: Consultant/Advisor: Genentech, Eisai, Halozyme Honoraria: Genentech, Celgene, Eisai, Prostrakan Research Funding: Medivation, AstraZeneca, Eisai, Ziopharm, Janssen, Genentech, Novartis.

All other authors have declared no conflicts of interest.