Phase 2 study of neoadjuvant enzalutamide and paclitaxel for luminal androgen receptor-enriched TNBC: Trial results and insights into “ARness”

Bora Lim; Sahil Seth; Clinton Yam; Lei Huo; Takeo Fujii; Jangsoon Lee; Roland Bassett; Sara Nasser; Lisa Ravenberg; Jason White; Alyson Clayborn; Gil Guerra; Jennifer K. Litton; Senthil Damodaran; Rachel Layman; Vicente Valero; Debasish Tripathy; Michael Lewis; Lacey E. Dobrolecki; Jonathan Lei; Rosalind Candelaria; Banu Arun; Gaiane Rauch; Li Zhao; Jianhua Zhang; Qingqing Ding; W. Fraser Symmans; Jeffrey T. Chang; Alastair M. Thompson; Stacy L. Moulder; Naoto T. Ueno

doi:10.1016/j.xcrm.2024.101595

Phase 2 study of neoadjuvant enzalutamide and paclitaxel for luminal androgen receptor-enriched TNBC: Trial results and insights into “ARness”

Bora Lim, Sahil Seth, Clinton Yam, Lei Huo, Takeo Fujii, Jangsoon Lee, Roland Bassett, Sara Nasser, Lisa Ravenberg, Jason White, Alyson Clayborn, Gil Guerra, Jennifer K. Litton, Senthil Damodaran, Rachel Layman, Vicente Valero, Debasish Tripathy, Michael Lewis, Lacey E. Dobrolecki, Jonathan LeiRosalind Candelaria, Banu Arun, Gaiane Rauch, Li Zhao, Jianhua Zhang, Qingqing Ding, W. Fraser Symmans, Jeffrey T. Chang, Alastair M. Thompson, Stacy L. Moulder, Naoto T. Ueno

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Abstract

Luminal androgen receptor (LAR)-enriched triple-negative breast cancer (TNBC) is a distinct subtype. The efficacy of AR inhibitors and the relevant biomarkers in neoadjuvant therapy (NAT) are yet to be determined. We tested the combination of the AR inhibitor enzalutamide (120 mg daily by mouth) and paclitaxel (80 mg/m² weekly intravenously) (ZT) for 12 weeks as NAT for LAR-enriched TNBC. Eligibility criteria included a percentage of cells expressing nuclear AR by immunohistochemistry (iAR) of at least 10% and a reduction in sonographic volume of less than 70% after four cycles of doxorubicin and cyclophosphamide. Twenty-four patients were enrolled. Ten achieved a pathologic complete response or residual cancer burden-I. ZT was safe, with no unexpected side effects. An iAR of at least 70% had a positive predictive value of 0.92 and a negative predictive value of 0.97 in predicting LAR-enriched TNBC according to RNA-based assays. Our data support future trials of AR blockade in early-stage LAR-enriched TNBC.

Original language	English (US)
Article number	101595
Journal	Cell Reports Medicine
Volume	5
Issue number	6
DOIs	https://doi.org/10.1016/j.xcrm.2024.101595
State	Published - Jun 18 2024

Keywords

ARness
LAR subtype
TNBC
androgen receptor
biomarker of response
enzalutamide
neoadjuvant systemic therapy
triple-negative breast cancer

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.xcrm.2024.101595

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Lim, B., Seth, S., Yam, C., Huo, L., Fujii, T., Lee, J., Bassett, R., Nasser, S., Ravenberg, L., White, J., Clayborn, A., Guerra, G., Litton, J. K., Damodaran, S., Layman, R., Valero, V., Tripathy, D., Lewis, M., Dobrolecki, L. E., ... Ueno, N. T. (2024). Phase 2 study of neoadjuvant enzalutamide and paclitaxel for luminal androgen receptor-enriched TNBC: Trial results and insights into “ARness”. Cell Reports Medicine, 5(6), Article 101595. https://doi.org/10.1016/j.xcrm.2024.101595

Lim, B, Seth, S, Yam, C , Huo, L, Fujii, T, Lee, J, Bassett, R, Nasser, S, Ravenberg, L, White, J, Clayborn, A, Guerra, G, Litton, JK , Damodaran, S , Layman, R , Valero, V , Tripathy, D, Lewis, M, Dobrolecki, LE, Lei, J, Candelaria, R , Arun, B , Rauch, G , Zhao, L, Zhang, J, Ding, Q , Symmans, WF, Chang, JT, Thompson, AM, Moulder, SL & Ueno, NT 2024, 'Phase 2 study of neoadjuvant enzalutamide and paclitaxel for luminal androgen receptor-enriched TNBC: Trial results and insights into “ARness”', Cell Reports Medicine, vol. 5, no. 6, 101595. https://doi.org/10.1016/j.xcrm.2024.101595

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title = "Phase 2 study of neoadjuvant enzalutamide and paclitaxel for luminal androgen receptor-enriched TNBC: Trial results and insights into “ARness”",

abstract = "Luminal androgen receptor (LAR)-enriched triple-negative breast cancer (TNBC) is a distinct subtype. The efficacy of AR inhibitors and the relevant biomarkers in neoadjuvant therapy (NAT) are yet to be determined. We tested the combination of the AR inhibitor enzalutamide (120 mg daily by mouth) and paclitaxel (80 mg/m2 weekly intravenously) (ZT) for 12 weeks as NAT for LAR-enriched TNBC. Eligibility criteria included a percentage of cells expressing nuclear AR by immunohistochemistry (iAR) of at least 10% and a reduction in sonographic volume of less than 70% after four cycles of doxorubicin and cyclophosphamide. Twenty-four patients were enrolled. Ten achieved a pathologic complete response or residual cancer burden-I. ZT was safe, with no unexpected side effects. An iAR of at least 70% had a positive predictive value of 0.92 and a negative predictive value of 0.97 in predicting LAR-enriched TNBC according to RNA-based assays. Our data support future trials of AR blockade in early-stage LAR-enriched TNBC.",

keywords = "ARness, LAR subtype, TNBC, androgen receptor, biomarker of response, enzalutamide, neoadjuvant systemic therapy, triple-negative breast cancer",

author = "Bora Lim and Sahil Seth and Clinton Yam and Lei Huo and Takeo Fujii and Jangsoon Lee and Roland Bassett and Sara Nasser and Lisa Ravenberg and Jason White and Alyson Clayborn and Gil Guerra and Litton, {Jennifer K.} and Senthil Damodaran and Rachel Layman and Vicente Valero and Debasish Tripathy and Michael Lewis and Dobrolecki, {Lacey E.} and Jonathan Lei and Rosalind Candelaria and Banu Arun and Gaiane Rauch and Li Zhao and Jianhua Zhang and Qingqing Ding and Symmans, {W. Fraser} and Chang, {Jeffrey T.} and Thompson, {Alastair M.} and Moulder, {Stacy L.} and Ueno, {Naoto T.}",

note = "Publisher Copyright: {\textcopyright} 2024 The Author(s)",

year = "2024",

month = jun,

day = "18",

doi = "10.1016/j.xcrm.2024.101595",

language = "English (US)",

volume = "5",

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T1 - Phase 2 study of neoadjuvant enzalutamide and paclitaxel for luminal androgen receptor-enriched TNBC

T2 - Trial results and insights into “ARness”

AU - Lim, Bora

AU - Seth, Sahil

AU - Yam, Clinton

AU - Huo, Lei

AU - Fujii, Takeo

AU - Lee, Jangsoon

AU - Bassett, Roland

AU - Nasser, Sara

AU - Ravenberg, Lisa

AU - White, Jason

AU - Clayborn, Alyson

AU - Guerra, Gil

AU - Litton, Jennifer K.

AU - Damodaran, Senthil

AU - Layman, Rachel

AU - Valero, Vicente

AU - Tripathy, Debasish

AU - Lewis, Michael

AU - Dobrolecki, Lacey E.

AU - Lei, Jonathan

AU - Candelaria, Rosalind

AU - Arun, Banu

AU - Rauch, Gaiane

AU - Zhao, Li

AU - Zhang, Jianhua

AU - Ding, Qingqing

AU - Symmans, W. Fraser

AU - Chang, Jeffrey T.

AU - Thompson, Alastair M.

AU - Moulder, Stacy L.

AU - Ueno, Naoto T.

PY - 2024/6/18

Y1 - 2024/6/18

N2 - Luminal androgen receptor (LAR)-enriched triple-negative breast cancer (TNBC) is a distinct subtype. The efficacy of AR inhibitors and the relevant biomarkers in neoadjuvant therapy (NAT) are yet to be determined. We tested the combination of the AR inhibitor enzalutamide (120 mg daily by mouth) and paclitaxel (80 mg/m2 weekly intravenously) (ZT) for 12 weeks as NAT for LAR-enriched TNBC. Eligibility criteria included a percentage of cells expressing nuclear AR by immunohistochemistry (iAR) of at least 10% and a reduction in sonographic volume of less than 70% after four cycles of doxorubicin and cyclophosphamide. Twenty-four patients were enrolled. Ten achieved a pathologic complete response or residual cancer burden-I. ZT was safe, with no unexpected side effects. An iAR of at least 70% had a positive predictive value of 0.92 and a negative predictive value of 0.97 in predicting LAR-enriched TNBC according to RNA-based assays. Our data support future trials of AR blockade in early-stage LAR-enriched TNBC.

AB - Luminal androgen receptor (LAR)-enriched triple-negative breast cancer (TNBC) is a distinct subtype. The efficacy of AR inhibitors and the relevant biomarkers in neoadjuvant therapy (NAT) are yet to be determined. We tested the combination of the AR inhibitor enzalutamide (120 mg daily by mouth) and paclitaxel (80 mg/m2 weekly intravenously) (ZT) for 12 weeks as NAT for LAR-enriched TNBC. Eligibility criteria included a percentage of cells expressing nuclear AR by immunohistochemistry (iAR) of at least 10% and a reduction in sonographic volume of less than 70% after four cycles of doxorubicin and cyclophosphamide. Twenty-four patients were enrolled. Ten achieved a pathologic complete response or residual cancer burden-I. ZT was safe, with no unexpected side effects. An iAR of at least 70% had a positive predictive value of 0.92 and a negative predictive value of 0.97 in predicting LAR-enriched TNBC according to RNA-based assays. Our data support future trials of AR blockade in early-stage LAR-enriched TNBC.

KW - ARness

KW - LAR subtype

KW - TNBC

KW - androgen receptor

KW - biomarker of response

KW - enzalutamide

KW - neoadjuvant systemic therapy

KW - triple-negative breast cancer

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AN - SCOPUS:85195885270

SN - 2666-3791

VL - 5

JO - Cell Reports Medicine

JF - Cell Reports Medicine

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M1 - 101595

ER -

Phase 2 study of neoadjuvant enzalutamide and paclitaxel for luminal androgen receptor-enriched TNBC: Trial results and insights into “ARness”

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Keywords

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