TBCRC 011: A Non-randomized, Single Agent, Open-label, Phase II Study of Bicalutamide in Patients with AR+, ER-/PR- Metastatic Breast Cancer (MBC)

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Purpose of the Study: 

Triple-negative breast cancer (TNBC) represents approximately 15% of all breast cancer but accounts for a disproportionate number of breast cancer-related deaths each year. TNBC are cancers that lack the three most common types of receptors known to fuel breast cancer: estrogen receptors (ER-), progesterone receptors (PR-) and HER2/neu (HER2-). Patients with TNBC have limited effective treatment options and generally experience poorer outcomes. Research at Memorial Sloan Kettering Cancer Center (MSKCC) has identified a subset of TNBC, which appears to have a similar underlying biology as ER- breast cancer.  Preclinical cell-culture and animal-model work has identified the role of the androgen receptor (AR) signaling pathway as a potential driver of tumor growth in this subset of cancers. We tested this hypothesis in this clinical trial of bicalutamide (an FDA-approved AR inhibitor for the treatment of prostate cancer) in AR+, ER-/PR- metastatic breast cancer (MBC). The purpose of this study was to test if bicalutamide can slow tumor growth and/or shrink tumors in patients with AR+, ER-/PR- MBC.


Memorial Sloan Kettering Cancer Center (MSKCC)

Participating Sites: 
  • Dana-Farber/ Harvard Cancer Center
  • Duke University Medical Cancer Center
  • Georgetown University
  • Mayo Clinic Cancer Center
  • Memorial Sloan Kettering Cancer Center
  • University of Alabama, Birmingham
  • University of California, San Francisco
  • University of North Carolina, Chapel Hill
Start Date & Stop Date: 

Date First Site Activated: MSKCC- March, 2007; Activated throughout the TBCRC in March, 2010

Date Trial Closed to Accrual: January, 2012

Key Eligibility Requirements: 

Eligibility for androgen receptor (AR) testing

  • Estrogen receptor/progesterone receptor negative (ER-/PR-) breast cancer
  • Locally advanced or metastatic disease

Eligibility for treatment with bicalutamide

  • Androgen receptor positive (AR+) (≥10%)
  • No limit to the number of prior therapies for MBC
  • Patients with HER2/neu positive breast cancer permitted if received prior trastuzumab
  • Age ≥18 years of age
  • Eastern Cooperative Oncology Group performance status < 2
  • Patients with brain metastases permitted if treated & stable ≥ 3months
  • Normal organ function
Study Design: 
  • TBCRC011 was initially opened at MSKCC and later expanded to 7 additional centers through the Translational Breast Cancer Research Consortium (TBCRC).
  • Primary objective was to evaluate the efficacy of oral bicalutamide, for the treatment of women with AR+, ER-/PR- MBC in terms of tumor shrinkage or prolonged stabilization of disease.
  • Additional objectives included (i) studying the safety and tolerability of the drug and (ii) correlative science studies (i.e. studying the relationship between biomarkers (genes and proteins) and disease progression using tissue samples).
  • Enrollment to this trial required 2 steps: (i) consent to determine AR status, which was permitted while on another therapy for breast cancer, followed by (ii) consent to receive therapy with bicalutamide for patients with confirmed AR+ ER-/PR- MBC.
  • All patients on the trial were treated with bicalutamide 150 mg orally daily. Patients underwent toxicity evaluation every 4 weeks and imaging to evaluate response to therapy every 12 weeks.
  • Twelve percent (51 of 424) of screened patients tested AR+.
  • Twenty-six study participants with AR+, ER-/PR- MBC were evaluable for the primary endpoint.
  • Five patients had stable disease > 6 months as their best response on treatment.
  • Final results published in Clinical Cancer Research (2013) demonstrated that this therapy is well-tolerated and can result in clinical benefit for patients with this subtype of breast cancer.
Next Steps: 
  • Ongoing correlative science projects from this study include the development of a novel genomic signature/biomarker to predict response to anti-androgen therapy in women with breast cancer.
  • Enzalutamide, is a next-generation pure AR antagonist which is FDA-approved for the treatment of advanced prostate cancer.
  • Results of the global phase 2 study of enzalutamide for the treatment of AR+ metastatic TNBC was recently presented (Traina et al ASCO 2015).
  • This trial, for which >400 women were screened at ~45 sites worldwide, demonstrated drug activity with the first ever objective responses reported as a result of an AR antagonist for the treatment of women with androgen-driven TNBC.
  • The TBCRC is now studying enzalutamide with or without a PI3 kinase inhibitor.
  • Building upon the results of TBCRC011, investigators at MSKCC are studying the combination of bicalutamide (AR inhibitor) and palbociclib, which reduces cancer cell division and proliferation, to evaluate whether treatment with both drugs will offer superior clinical outcomes for AR-dependent breast cancer.
  • Additionally, building upon this work, the TBCRC is conducting companion correlative studies to better describe the biology of AR+ breast cancer and exploring other novel new drugs to target androgens.
  • Furthermore, several novel therapies targeting AR are currently undergoing evaluation in clinical trials either as monotherapy or in combination with other targeted agents.
Scientific Publications Available for this Clinical Trial: 

Gucalp, A.,  Tolaney, S.M.,  Isakoff, S.J.,  Ingle, J.N., Liu, M.C., Carey, L.A., Blackwell, K.L., Rugo, H.S.,  Nabell, L., Abbruzzi, A., Gonzalez, J., Giri, D.D., Patil, S., Feigin, K., D'Andrea, G., Theodoulou, M., Drullinsky, P., Sklarin, N.T.,  Hudis, C., Traina, T.A. TBCRC 011: Targeting the androgen receptor (AR) for the treatment of AR+/ER-/PR- metastatic breast cancer (MBC). 2011 ASCO, Trials in Progress Poster, Abstract #TPS122.

Gucalp, A., Tolaney, S., Isakoff, S., Ingle, J., Liu, M.C., Carey, L., Blackwell, K., Rugo, H., Nabell, L., Forero, A., Stearns, V., Momen, L., Gonzalez, J., Giri, D., Patil, S., Feigin, K., Hudis, C.A., Traina, T.A. Targeting the androgen receptor (AR) in women with AR+ ER-/PR- metastatic breast cancer (MBC). 2012 ASCO, Oral Presentation, Abstract #1006.

Gucalp, A., Tolaney, S.,  Isakoff, S., Ingle, J.,  Liu, M.,  Carey, L,  Blackwell, K., Rugo, H.,  Nabell, L.,  Forero, A., Stearns, V.,  Momen, L., Gonzalez, J.,  Akhtar, A.,  Giri, D.,  Patil, S.,  Feigin, K.,  Hudis, C.,  Traina, T.A. Endocrine biomarkers in response to AR-inhibition with bicalutamide for the treatment of AR(+), ER/PR(-) metastatic breast cancer (MBC) (TBCRC011). 2012 SABCS, Poster P6-05-02.

Gucalp, A.,  Tolaney, S.,  Isakoff, S.J.,   Ingle, J.N., Liu, M.C.,   Carey, L.A.,  Blackwell, K.,  Rugo, H.,  Nabell, L., Forero, A.,  Stearns, V.,   Doane, A.S.,  Danso, M., Moynahan, M.E.,  Momen, L.F.,  Gonzalez, J.M.,  Akhtar, A., Giri, D.D.,  Patil, S.,  Feigin, K.N.,  Hudis, C.A.,  Traina T.A.  Phase II Trial of Bicalutamide in Patients with Androgen Receptor Positive, Hormone Receptor Negative Metastatic Breast Cancer. Clin Cancer Res 19(19): 2013.

Traina, T.A., Gucalp, A., Polkinghorn, W., Isakoff, S., Tolaney, S., Carey, L., Ingle, J., Nabell, L., Forero-Torres, A., Rugo, H., Blackwell, K., Liu, M.,  Soloway, M., Mose, L.,  Giri, D., Bhanot, U., Viale, A., Hudis, C., Sawyers, C., Parker, J. Whole transcriptome analysis of AR+ ER/PR- metastatic breast cancers treated with bicalutamide on TBCRC011. 2014 SABCS, Poster, Abstract #277.

 *This summary was reviewed by: Tiffany Traina, M.D. and Ayca Gucalp, M.D.  This summary was also reviewed and approved by the members of the TBCRC Patient Advocate Working Group.