BackgroundGiredestrant, a highly potent, non-steroidal, oral, selective ER antagonist and degrader (SERD), has shown encouraging antitumour activity as monotherapy and + P in metastatic BC. In coopERA BC (NCT04436744), the primary endpoint of superior suppression of Ki67 with single-agent giredestrant vs A from baseline (BL) after 2 weeks of treatment for ER+/HER2– eBC was met. Here, we report biomarker subgroup analyses of potential associations between BL characteristics, clinical features and Ki67 reduction.Methods221 patients with cT1c (≥1.5 cm)–cT4a–c ER+/HER2– eBC and BL Ki67 score ≥5% were randomised 1:1 to receive giredestrant or A alone for 14 days (D), then + P for four 28-D cycles. The primary outcome of Ki67 change from BL to Week 2 was analysed based on AJCC stage, primary tumour stage, nodal (N) status, histological grade or subtype and progesterone receptor (PgR) status. Changes in ER/PgR protein levels were assessed by H-score.ResultsTable: 144P% Ki67 reductionAGiredestrantAJCC stageI6675II6875III6274Primary tumour stageT16473T26876T36580T46965N statuscN05972cN+5979Histological grade1/2677636668Histological subtypeDuctal6576Lobular6871PgR status+7077–3960 Open table in a new tab ConclusionsGiredestrant induced greater suppression of Ki67 than A in ER+/HER2– eBC regardless of stage, histological subtype and PgR status, providing rationale for further evaluation in the adjuvant setting.Clinical trial identificationNCT04436744 (June 18, 2020).Editorial acknowledgementSupport for third-party writing assistance for this abstract, furnished by Martin Cadogan, PhD, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland.Legal entity responsible for the studyF. Hoffmann-La Roche Ltd.FundingF. Hoffmann-La Roche Ltd.DisclosureA. Bardia: Financial Interests, Personal, Advisory Board: Pfizer , Novartis , Genentech , Merck , Radius Health , Immunomedics, Taiho, Sanofi , Daiichi Pharma/ AstraZeneca , Puma, Biotheranostics Inc., Phillips, Eli Lilly , Foundation Medicine; Financial Interests, Institutional, Research Grant: Genetech, Novartis , Pfizer , Merck , Sanofi , Radius Health , Immunomedics, Daiichi Pharma/AstraZeneca; Non-Financial Interests, Personal, Research Grant, Medical writing support for this abstract, furnished by Martin Cadogan, PhD, of Health Interactions, was funded by F. Hoffmann-La Roche Ltd.: F. Hoffmann-La Roche Ltd. T.M. Fernando: Financial Interests, Personal, Full or part-time Employment: Genentech, Inc.; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd; Non-Financial Interests, Personal, Research Grant, Medical writing support for this abstract, furnished by Martin Cadogan, PhD, of Health Interactions, was funded by F. Hoffmann-La Roche Ltd.: F. Hoffmann-La Roche Ltd. P.A. Fasching: Financial Interests, Personal, Advisory Board: Novartis, Pfizer, Daiichi Sankyo, AstraZeneca, Eisai, Merck Sharp & Dohme, Lilly, Pierre Fabre, SeaGen, F. Hoffmann-La Roche Ltd, Hexal, Agendia, Gilead; Financial Interests, Personal, Invited Speaker: Novartis, Pfizer, Daiichi Sankyo, AstraZeneca, Eisai, Merck Sharp & Dohme, Lilly, SeaGen, F. Hoffmann-La Roche Ltd, Gilead; Financial Interests, Institutional, Research Grant: Biontech, Cepheid; Financial Interests, Personal, Research Grant, Medical writing support for this abstract, furnished by Martin Cadogan, PhD, of Health Interactions, was funded by F. Hoffmann-La Roche Ltd.: F. Hoffmann-La Roche Ltd. V. Quiroga Garcia: Financial Interests, Personal, Other, Honoraria: F. Hoffmann-La Roche Ltd, Pfizer; Financial Interests, Institutional, Research Grant: Celgene; Financial Interests, Personal, Other, Travel/accommodation/ expenses: Novartis , F. Hoffmann-La Roche Ltd; Financial Interests, Institutional, Funding: Celgene; Non-Financial Interests, Personal, Research Grant, Medical writing support for this abstract, furnished by Martin Cadogan, PhD, of Health Interactions, was funded by F. Hoffmann-La Roche Ltd.: F. Hoffmann-La Roche Ltd. Y.H. Park: Non-Financial Interests, Personal, Advisory Board: AstraZeneca, Pfizer, F. Hoffmann-La Roche Ltd, Novartis , Eisai , Lilly; Financial Interests, Institutional, Research Grant, Contracted research: AstraZeneca , Pfizer , F. Hoffmann-La Roche Ltd, Merck; Non-Financial Interests, Institutional, Principal Investigator, Contracted research: AstraZeneca, Pfizer, F. Hoffmann-La Roche Ltd, Novartis; Financial Interests, Personal, Other, Speaker fee: F. Hoffmann-La Roche Ltd, Novartis; Financial Interests, Institutional, Principal Investigator, Contracted research: Daiichi Sankyo, Merck; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Institutional, Research Grant: Gencurix; Non-Financial Interests, Personal, Research Grant, Medical writing support for this abstract, furnished by Martin Cadogan, PhD, of Health Interactions, was funded by F. Hoffmann-La Roche Ltd.: F. Hoffmann-La Roche Ltd. J.M. Giltnane: Financial Interests, Personal, Full or part-time Employment: Genentech, Inc.; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd; Non-Financial Interests, Personal, Research Grant, Medical writing support for this abstract, furnished by Martin Cadogan, PhD, of Health Interactions, was funded by F. Hoffmann-La Roche Ltd.: F. Hoffmann-La Roche Ltd. C. Xue: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd; Non-Financial Interests, Personal, Research Grant, Medical writing support for this abstract, furnished by Martin Cadogan, PhD, of Health Interactions, was funded by F. Hoffmann-La Roche Ltd.: F. Hoffmann-La Roche Ltd. V. Lopez Valverde: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd; Non-Financial Interests, Personal, Research Grant, Medical writing support for this abstract, furnished by Martin Cadogan, PhD, of Health Interactions, was funded by F. Hoffmann-La Roche Ltd.: F. Hoffmann-La Roche Ltd. J. Steinseifer-Szabo: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd; Non-Financial Interests, Personal, Research Grant, Medical writing support for this abstract, furnished by Martin Cadogan, PhD, of Health Interactions, was funded by F. Hoffmann-La Roche Ltd.: F. Hoffmann-La Roche Ltd. P.D. Pérez-Moreno: Financial Interests, Personal, Full or part-time Employment: Genentech, Inc.; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd; Non-Financial Interests, Personal, Research Grant, Medical writing support for this abstract, furnished by Martin Cadogan, PhD, of Health Interactions, was funded by F. Hoffmann-La Roche Ltd.: F. Hoffmann-La Roche Ltd. H.M. Moore: Financial Interests, Personal, Full or part-time Employment: Genentech, Inc.; Financial Interests, Personal, Full or part-time Employment, Spouse: Pfizer; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd; Non-Financial Interests, Personal, Research Grant, Medical writing support for this abstract, furnished by Martin Cadogan, PhD, of Health Interactions, was funded by F. Hoffmann-La Roche Ltd.: F. Hoffmann-La Roche Ltd. S.A. Hurvitz: Financial Interests, Institutional, Research Grant, Contracted research: Ambrx, Amgen , AstraZeneca , Arvinas, Bayer , Cytomx, Daiichi Sankyo, Dignitana, Genentech /F. Hoffmann-La Roche Ltd, Gilead, GSK, Immunomedics, Lilly, Macrogenics, Novartis, Pfizer, OBI Pharma, Orinove, Pieris, PUMA, Radius, Sanofi, Seattle Genetics/Seagen, Zymeworks, Phoenix Molecular Designs, Ltd; Financial Interests, Personal, Other, Travel accommodations, expenses (2019): Lilly; Financial Interests, Personal, Stocks/Shares, Spouse: Ideal Plant; Financial Interests, Personal, Stocks/Shares: NKMax; Financial Interests, Personal, Advisory Board: Daiichi Sankyo/ AstraZeneca, Genentech/F. Hoffmann-La Roche Ltd, Novartis , Sanofi; Non-Financial Interests, Personal, Research Grant, Medical writing support for this abstract, furnished by Martin Cadogan, PhD, of Health Interactions, was funded by F. Hoffmann-La Roche Ltd.: F. Hoffmann-La Roche Ltd. BackgroundGiredestrant, a highly potent, non-steroidal, oral, selective ER antagonist and degrader (SERD), has shown encouraging antitumour activity as monotherapy and + P in metastatic BC. In coopERA BC (NCT04436744), the primary endpoint of superior suppression of Ki67 with single-agent giredestrant vs A from baseline (BL) after 2 weeks of treatment for ER+/HER2– eBC was met. Here, we report biomarker subgroup analyses of potential associations between BL characteristics, clinical features and Ki67 reduction. Giredestrant, a highly potent, non-steroidal, oral, selective ER antagonist and degrader (SERD), has shown encouraging antitumour activity as monotherapy and + P in metastatic BC. In coopERA BC (NCT04436744), the primary endpoint of superior suppression of Ki67 with single-agent giredestrant vs A from baseline (BL) after 2 weeks of treatment for ER+/HER2– eBC was met. Here, we report biomarker subgroup analyses of potential associations between BL characteristics, clinical features and Ki67 reduction. Methods221 patients with cT1c (≥1.5 cm)–cT4a–c ER+/HER2– eBC and BL Ki67 score ≥5% were randomised 1:1 to receive giredestrant or A alone for 14 days (D), then + P for four 28-D cycles. The primary outcome of Ki67 change from BL to Week 2 was analysed based on AJCC stage, primary tumour stage, nodal (N) status, histological grade or subtype and progesterone receptor (PgR) status. Changes in ER/PgR protein levels were assessed by H-score. 221 patients with cT1c (≥1.5 cm)–cT4a–c ER+/HER2– eBC and BL Ki67 score ≥5% were randomised 1:1 to receive giredestrant or A alone for 14 days (D), then + P for four 28-D cycles. The primary outcome of Ki67 change from BL to Week 2 was analysed based on AJCC stage, primary tumour stage, nodal (N) status, histological grade or subtype and progesterone receptor (PgR) status. Changes in ER/PgR protein levels were assessed by H-score. ResultsTable: 144P% Ki67 reductionAGiredestrantAJCC stageI6675II6875III6274Primary tumour stageT16473T26876T36580T46965N statuscN05972cN+5979Histological grade1/2677636668Histological subtypeDuctal6576Lobular6871PgR status+7077–3960 Open table in a new tab ConclusionsGiredestrant induced greater suppression of Ki67 than A in ER+/HER2– eBC regardless of stage, histological subtype and PgR status, providing rationale for further evaluation in the adjuvant setting. Giredestrant induced greater suppression of Ki67 than A in ER+/HER2– eBC regardless of stage, histological subtype and PgR status, providing rationale for further evaluation in the adjuvant setting.