Enzalutamide for the treatment of androgen receptor-expressing triple-negative breast cancer

Tiffany A. Traina, Kathy Miller, Denise A. Yardley, Janice Eakle, Lee S. Schwartzberg, Joyce O'Shaughnessy, William Gradishar, Peter Schmid, Eric Winer, Catherine Kelly, Rita Nanda, Ayca Gucalp, Ahmad Awada, Laura Garcia-Estevez, Maureen E. Trudeau, Joyce Steinberg, Hirdesh Uppal, Iulia Cristina Tudor, Amy Peterson, Javier Cortes

Research output: Contribution to journalArticle

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Abstract

Purpose Studies suggest that a subset of patients with triple-negative breast cancer (TNBC) have tumors that express the androgen receptor (AR) and may benefit from an AR inhibitor. This phase II study evaluated the antitumor activity and safety of enzalutamide in patients with locally advanced or metastatic AR-positive TNBC. Patients and Methods Tumors were tested for AR with an immunohistochemistry assay optimized for breast cancer; nuclear AR staining . 0% was considered positive. Patients received enzalutamide 160 mg once per day until disease progression. The primary end point was clinical benefit rate (CBR) at 16 weeks. Secondary end points included CBR at 24 weeks, progression-free survival, and safety. End points were analyzed in all enrolled patients (the intent-to-treat [ITT] population) and in patients with one or more postbaseline assessment whose tumor expressed $ 10% nuclear AR (the evaluable subgroup). Results Of 118 patients enrolled, 78 were evaluable. CBR at 16 weeks was 25% (95% CI, 17% to 33%) in the ITT population and 33% (95% CI, 23% to 45%) in the evaluable subgroup. Median progression-free survival was 2.9 months (95% CI, 1.9 to 3.7 months) in the ITT population and 3.3 months (95% CI, 1.9 to 4.1 months) in the evaluable subgroup. Median overall survival was 12.7 months (95% CI, 8.5 months to not yet reached) in the ITT population and 17.6 months (95% CI, 11.6 months to not yet reached) in the evaluable subgroup. Fatigue was the only treatment-related grade 3 or higher adverse event with an incidence of . 2%. Conclusion Enzalutamide demonstrated clinical activity and was well tolerated in patients with advanced AR-positive TNBC. Adverse events related to enzalutamide were consistent with its known safety profile. This study supports additional development of enzalutamide in advanced TNBC.

Original languageEnglish (US)
Pages (from-to)884-890
Number of pages7
JournalJournal of Clinical Oncology
Volume36
Issue number9
DOIs
StatePublished - Jan 1 2018

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Triple Negative Breast Neoplasms
Androgen Receptors
Therapeutics
Cytoplasmic and Nuclear Receptors
Safety
Population
Disease-Free Survival
Neoplasms
MDV 3100
Fatigue
Disease Progression
Immunohistochemistry
Staining and Labeling
Breast Neoplasms
Survival

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Traina, T. A., Miller, K., Yardley, D. A., Eakle, J., Schwartzberg, L. S., O'Shaughnessy, J., ... Cortes, J. (2018). Enzalutamide for the treatment of androgen receptor-expressing triple-negative breast cancer. Journal of Clinical Oncology, 36(9), 884-890. https://doi.org/10.1200/JCO.2016.71.3495

Enzalutamide for the treatment of androgen receptor-expressing triple-negative breast cancer. / Traina, Tiffany A.; Miller, Kathy; Yardley, Denise A.; Eakle, Janice; Schwartzberg, Lee S.; O'Shaughnessy, Joyce; Gradishar, William; Schmid, Peter; Winer, Eric; Kelly, Catherine; Nanda, Rita; Gucalp, Ayca; Awada, Ahmad; Garcia-Estevez, Laura; Trudeau, Maureen E.; Steinberg, Joyce; Uppal, Hirdesh; Tudor, Iulia Cristina; Peterson, Amy; Cortes, Javier.

In: Journal of Clinical Oncology, Vol. 36, No. 9, 01.01.2018, p. 884-890.

Research output: Contribution to journalArticle

Traina, TA, Miller, K, Yardley, DA, Eakle, J, Schwartzberg, LS, O'Shaughnessy, J, Gradishar, W, Schmid, P, Winer, E, Kelly, C, Nanda, R, Gucalp, A, Awada, A, Garcia-Estevez, L, Trudeau, ME, Steinberg, J, Uppal, H, Tudor, IC, Peterson, A & Cortes, J 2018, 'Enzalutamide for the treatment of androgen receptor-expressing triple-negative breast cancer', Journal of Clinical Oncology, vol. 36, no. 9, pp. 884-890. https://doi.org/10.1200/JCO.2016.71.3495
Traina, Tiffany A. ; Miller, Kathy ; Yardley, Denise A. ; Eakle, Janice ; Schwartzberg, Lee S. ; O'Shaughnessy, Joyce ; Gradishar, William ; Schmid, Peter ; Winer, Eric ; Kelly, Catherine ; Nanda, Rita ; Gucalp, Ayca ; Awada, Ahmad ; Garcia-Estevez, Laura ; Trudeau, Maureen E. ; Steinberg, Joyce ; Uppal, Hirdesh ; Tudor, Iulia Cristina ; Peterson, Amy ; Cortes, Javier. / Enzalutamide for the treatment of androgen receptor-expressing triple-negative breast cancer. In: Journal of Clinical Oncology. 2018 ; Vol. 36, No. 9. pp. 884-890.
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abstract = "Purpose Studies suggest that a subset of patients with triple-negative breast cancer (TNBC) have tumors that express the androgen receptor (AR) and may benefit from an AR inhibitor. This phase II study evaluated the antitumor activity and safety of enzalutamide in patients with locally advanced or metastatic AR-positive TNBC. Patients and Methods Tumors were tested for AR with an immunohistochemistry assay optimized for breast cancer; nuclear AR staining . 0{\%} was considered positive. Patients received enzalutamide 160 mg once per day until disease progression. The primary end point was clinical benefit rate (CBR) at 16 weeks. Secondary end points included CBR at 24 weeks, progression-free survival, and safety. End points were analyzed in all enrolled patients (the intent-to-treat [ITT] population) and in patients with one or more postbaseline assessment whose tumor expressed $ 10{\%} nuclear AR (the evaluable subgroup). Results Of 118 patients enrolled, 78 were evaluable. CBR at 16 weeks was 25{\%} (95{\%} CI, 17{\%} to 33{\%}) in the ITT population and 33{\%} (95{\%} CI, 23{\%} to 45{\%}) in the evaluable subgroup. Median progression-free survival was 2.9 months (95{\%} CI, 1.9 to 3.7 months) in the ITT population and 3.3 months (95{\%} CI, 1.9 to 4.1 months) in the evaluable subgroup. Median overall survival was 12.7 months (95{\%} CI, 8.5 months to not yet reached) in the ITT population and 17.6 months (95{\%} CI, 11.6 months to not yet reached) in the evaluable subgroup. Fatigue was the only treatment-related grade 3 or higher adverse event with an incidence of . 2{\%}. Conclusion Enzalutamide demonstrated clinical activity and was well tolerated in patients with advanced AR-positive TNBC. Adverse events related to enzalutamide were consistent with its known safety profile. This study supports additional development of enzalutamide in advanced TNBC.",
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AU - Traina, Tiffany A.

AU - Miller, Kathy

AU - Yardley, Denise A.

AU - Eakle, Janice

AU - Schwartzberg, Lee S.

AU - O'Shaughnessy, Joyce

AU - Gradishar, William

AU - Schmid, Peter

AU - Winer, Eric

AU - Kelly, Catherine

AU - Nanda, Rita

AU - Gucalp, Ayca

AU - Awada, Ahmad

AU - Garcia-Estevez, Laura

AU - Trudeau, Maureen E.

AU - Steinberg, Joyce

AU - Uppal, Hirdesh

AU - Tudor, Iulia Cristina

AU - Peterson, Amy

AU - Cortes, Javier

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N2 - Purpose Studies suggest that a subset of patients with triple-negative breast cancer (TNBC) have tumors that express the androgen receptor (AR) and may benefit from an AR inhibitor. This phase II study evaluated the antitumor activity and safety of enzalutamide in patients with locally advanced or metastatic AR-positive TNBC. Patients and Methods Tumors were tested for AR with an immunohistochemistry assay optimized for breast cancer; nuclear AR staining . 0% was considered positive. Patients received enzalutamide 160 mg once per day until disease progression. The primary end point was clinical benefit rate (CBR) at 16 weeks. Secondary end points included CBR at 24 weeks, progression-free survival, and safety. End points were analyzed in all enrolled patients (the intent-to-treat [ITT] population) and in patients with one or more postbaseline assessment whose tumor expressed $ 10% nuclear AR (the evaluable subgroup). Results Of 118 patients enrolled, 78 were evaluable. CBR at 16 weeks was 25% (95% CI, 17% to 33%) in the ITT population and 33% (95% CI, 23% to 45%) in the evaluable subgroup. Median progression-free survival was 2.9 months (95% CI, 1.9 to 3.7 months) in the ITT population and 3.3 months (95% CI, 1.9 to 4.1 months) in the evaluable subgroup. Median overall survival was 12.7 months (95% CI, 8.5 months to not yet reached) in the ITT population and 17.6 months (95% CI, 11.6 months to not yet reached) in the evaluable subgroup. Fatigue was the only treatment-related grade 3 or higher adverse event with an incidence of . 2%. Conclusion Enzalutamide demonstrated clinical activity and was well tolerated in patients with advanced AR-positive TNBC. Adverse events related to enzalutamide were consistent with its known safety profile. This study supports additional development of enzalutamide in advanced TNBC.

AB - Purpose Studies suggest that a subset of patients with triple-negative breast cancer (TNBC) have tumors that express the androgen receptor (AR) and may benefit from an AR inhibitor. This phase II study evaluated the antitumor activity and safety of enzalutamide in patients with locally advanced or metastatic AR-positive TNBC. Patients and Methods Tumors were tested for AR with an immunohistochemistry assay optimized for breast cancer; nuclear AR staining . 0% was considered positive. Patients received enzalutamide 160 mg once per day until disease progression. The primary end point was clinical benefit rate (CBR) at 16 weeks. Secondary end points included CBR at 24 weeks, progression-free survival, and safety. End points were analyzed in all enrolled patients (the intent-to-treat [ITT] population) and in patients with one or more postbaseline assessment whose tumor expressed $ 10% nuclear AR (the evaluable subgroup). Results Of 118 patients enrolled, 78 were evaluable. CBR at 16 weeks was 25% (95% CI, 17% to 33%) in the ITT population and 33% (95% CI, 23% to 45%) in the evaluable subgroup. Median progression-free survival was 2.9 months (95% CI, 1.9 to 3.7 months) in the ITT population and 3.3 months (95% CI, 1.9 to 4.1 months) in the evaluable subgroup. Median overall survival was 12.7 months (95% CI, 8.5 months to not yet reached) in the ITT population and 17.6 months (95% CI, 11.6 months to not yet reached) in the evaluable subgroup. Fatigue was the only treatment-related grade 3 or higher adverse event with an incidence of . 2%. Conclusion Enzalutamide demonstrated clinical activity and was well tolerated in patients with advanced AR-positive TNBC. Adverse events related to enzalutamide were consistent with its known safety profile. This study supports additional development of enzalutamide in advanced TNBC.

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