Phase II trial of bicalutamide in patients with androgen receptor-positive, estrogen receptor-negative metastatic Breast Cancer
Ayca Gucalp, Sara Tolaney, Steven J Isakoff, James N Ingle, Minetta C Liu, Lisa A Carey, Kimberly Blackwell, Hope Rugo, Lisle Nabell, Andres Forero, Vered Stearns, Ashley S Doane, Michael Danso, Mary Ellen Moynahan, Lamia F Momen, Joseph M Gonzalez, Arooj Akhtar, Dilip D Giri, Sujata Patil, Kimberly N Feigin, Clifford A Hudis, Tiffany A Traina, Translational Breast Cancer Research Consortium (TBCRC 011), Ayca Gucalp, Sara Tolaney, Steven J Isakoff, James N Ingle, Minetta C Liu, Lisa A Carey, Kimberly Blackwell, Hope Rugo, Lisle Nabell, Andres Forero, Vered Stearns, Ashley S Doane, Michael Danso, Mary Ellen Moynahan, Lamia F Momen, Joseph M Gonzalez, Arooj Akhtar, Dilip D Giri, Sujata Patil, Kimberly N Feigin, Clifford A Hudis, Tiffany A Traina, Translational Breast Cancer Research Consortium (TBCRC 011)
Abstract
Purpose: Patients with hormone receptor-negative breast cancer generally do not benefit from endocrine-targeted therapies. However, a subset with androgen receptor (AR) expression is predicted to respond to antiandrogen therapies. This phase II study explored bicalutamide in AR-positive, estrogen receptor (ER), and progesterone receptor (PgR)-negative metastatic breast cancer.
Experimental design: Tumors from patients with ER/PgR-negative advanced breast cancer were tested centrally for AR [immunohistochemistry (IHC) > 10% nuclear staining considered positive]. If either the primary or a metastatic site was positive, patients were eligible to receive the AR antagonist bicalutamide at a dose of 150 mg daily. Clinical benefit rate (CBR), the primary endpoint, was defined as the total number of patients who show a complete response (CR), partial response (PR), or stable disease (SD) > 6 months; secondary endpoints included progression-free survival (PFS) and toxicity. Correlative studies included measurement of circulating endocrine markers and IHC surrogates for basal-like breast cancer.
Results: Of 424 patients with ER/PgR-negative breast cancer, 12% tested AR-positive. The 6-month CBR was 19% [95% confidence interval (CI), 7%-39%] for bicalutamide. The median PFS was 12 weeks (95% CI, 11-22 weeks). Bicalutamide was well-tolerated with no grade 4/5 treatment-related adverse events observed.
Conclusion: AR was expressed in 12% of patients with ER/PgR-negative breast cancer screened for this trial. The CBR of 19% observed with bicalutamide shows proof of principle for the efficacy of minimally toxic androgen blockade in a select group of patients with ER/PgR-negative, AR-positive breast cancer.
Conflict of interest statement
Disclosure of Potential Conflicts of Interest
No potential conflicts of interest were disclosed by the other authors.
©2013 AACR.
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Source: PubMed