LBA14 - Neoadjuvant giredestrant (GDC-9545) + palbociclib (palbo) vs anastrozole (A) + palbo in post-menopausal women with oestrogen receptor-positive, HER2-negative, untreated early breast cancer (ER+/HER2– eBC): Interim analysis of the randomised, open-label, phase II coopERA BC study

Background

Endocrine therapy is the mainstay for ER+ BC while CDK4/6 inhibitors + A decrease Ki67 expression (a proliferation biomarker). Giredestrant, a highly potent, nonsteroidal, oral, selective ER antagonist and degrader (SERD), achieves robust ER occupancy, is well tolerated and has encouraging anti-tumour activity as monotherapy and in combination with palbo in metastatic BC. coopERA BC (NCT04436744) investigates giredestrant vs A (both + palbo) in post-menopausal women with ER+/HER2– eBC. We present an interim analysis.

Methods

Patients (pts) with measurable cT1c (≥1.5 cm)–cT4a–c ER+/HER2– eBC and baseline Ki67 score ≥5% are randomised 1:1 to 1 mg oral daily (PO QD) A or 30 mg PO QD giredestrant on Days (D)1–14 (window-of-opportunity [WOO] phase; 14D) followed by QD dosing for four 28-D cycles + 125 mg PO palbo on D1–21 (neoadjuvant phase; 16 weeks) pre-surgery. Stratification factors: T status; Ki67 score; progesterone receptor status. Primary efficacy endpoint: Centrally assessed geometric mean relative Ki67 score change from baseline to Week 2 during the WOO phase (scores reflect endocrine therapies’ ability to suppress proliferation; a surrogate clinical outcomes marker). Complete cell cycle arrest rate (CCCA; pts with Ki67 score ≤2.7%) at Week 2 is a secondary efficacy endpoint. Safety is also assessed.

Results

83/202 planned pts were assessed. Two-week relative Ki67 reduction was greater with giredestrant (reduction from baseline to Week 2 geometric mean = 80%; 95% CI = 72%, 85%) than A (67%; 95% CI = 56%, 75%; P = 0.0222). Consistent Ki67 suppression was observed in pts with baseline Ki67 ≥20% (giredestrant: 83% reduction; A: 71%) or <20% (65% vs 24%). At Week 2, 25% of tumours exhibited CCCA with giredestrant vs 5% with A (Δ 20%; 95% CI = –37%, –3%). Fewer pts had giredestrant- vs A-related adverse events (AEs) (28% vs 38%); no grade ≥3 AEs or serious AEs were giredestrant-related.

Conclusions

Interim analysis data demonstrated superior anti-proliferative activity of giredestrant compared with A. Safety was consistent with the known giredestrant profile.

Clinical trial identification

NCT04436744.

Editorial acknowledgement

Medical writing support for this abstract, furnished by Daniel Clyde, PhD, and Bonnie Jordan, BSc, of Health Interactions, was funded by F. Hoffmann-La Roche Ltd.

Legal entity responsible for the study

F. Hoffmann-La Roche Ltd.

Funding

F. Hoffmann-La Roche Ltd.

Disclosure

S.A. Hurvitz: Financial Interests, Institutional, Research Grant, Contracted research: Ambrx; Financial Interests, Institutional, Research Grant, Contracted research: Amgen; Financial Interests, Institutional, Research Grant, Contracted research: AstraZeneca; Financial Interests, Institutional, Research Grant, Contracted research: Arvinas; Financial Interests, Institutional, Research Grant, Contracted research: Bayer; Financial Interests, Institutional, Research Grant, Contracted research: Daiichi Sankyo; Financial Interests, Institutional, Research Grant, Contracted research: Genentech/Roche; Financial Interests, Institutional, Research Grant, Contracted research: Gilead; Financial Interests, Institutional, Research Grant, Contracted research: GSK; Financial Interests, Institutional, Research Grant, Contracted research: Immunomedics; Financial Interests, Institutional, Research Grant, Contracted research: Lilly; Financial Interests, Institutional, Research Grant, Contracted research: Macrogenics; Financial Interests, Institutional, Research Grant, Contracted research: Novartis; Financial Interests, Institutional, Research Grant, Contracted research: Pfizer; Financial Interests, Institutional, Research Grant, Contracted research: OBI Pharma; Financial Interests, Institutional, Research Grant, Contracted research: Pieris; Financial Interests, Institutional, Research Grant, Contracted research: PUMA; Financial Interests, Institutional, Research Grant, Contracted research: Radius; Financial Interests, Institutional, Research Grant, Contracted research: Sanofi; Financial Interests, Institutional, Research Grant, Contracted research: Seattle Genetics; Financial Interests, Institutional, Research Grant, Contracted research: Dignitana; Financial Interests, Institutional, Research Grant, Contracted research: Zymeworks; Financial Interests, Institutional, Research Grant, Contracted research: Phoenix Molecular Designs, Ltd; Financial Interests, Personal, Other, Travel (2019): Lilly; Financial Interests, Personal, Stocks/Shares, Spouse: Ideal Implant; Financial Interests, Personal, Stocks/Shares: NKMax; Non-Financial Interests, Personal, Research Grant, Medical writing support: F. Hoffmann-La Roche Ltd. Y.H. Park: Non-Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Institutional, Research Grant, Contracted research: AstraZeneca; Non-Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Institutional, Research Grant, Contracted research: Pfizer; Non-Financial Interests, Institutional, Principal Investigator, Contracted research: AstraZeneca; Non-Financial Interests, Institutional, Principal Investigator, Contracted research: Pfizer; Non-Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Institutional, Research Grant, Contracted research: Roche; Non-Financial Interests, Institutional, Principal Investigator, Contracted research: Roche; Financial Interests, Personal, Other, Speaker fee: Roche; Non-Financial Interests, Institutional, Principal Investigator, Contracted research: Daiichi Sankyo; Non-Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Other, Speaker fee: Novartis; Non-Financial Interests, Institutional, Principal Investigator, Contracted research: Novartis; Non-Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Institutional, Research Grant, Contracted research: Merck; Non-Financial Interests, Institutional, Principal Investigator, Contracted research: Merck; Non-Financial Interests, Personal, Research Grant, Medical writing support: F. Hoffmann-La Roche Ltd. A. Bardia: Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Genentech; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Radius Health; Financial Interests, Personal, Advisory Board: Immunomedics; Financial Interests, Personal, Advisory Board: Taiho; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Advisory Board: Daiichi Pharma/AstraZeneca; Financial Interests, Personal, Advisory Board: Puma; Financial Interests, Personal, Advisory Board: Biotheranostics Inc.; Financial Interests, Personal, Advisory Board: Phillips; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Advisory Board: Foundation Medicine; Financial Interests, Institutional, Research Grant: Genentech; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: Sanofi; Financial Interests, Institutional, Research Grant: Radius Health; Financial Interests, Institutional, Research Grant: Immunomedics; Financial Interests, Institutional, Research Grant: Daiichi Pharma/AstraZeneca; Non-Financial Interests, Personal, Research Grant, Medical writing support: F. Hoffmann-La Roche Ltd. V. Quiroga: Financial Interests, Personal, Other, Honoraria: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Other, Honoraria: Pfizer; Financial Interests, Institutional, Research Grant: Celgene; Financial Interests, Personal, Other, Travel/accommodation/ expenses: Novartis; Financial Interests, Institutional, Funding: Celgene; Non-Financial Interests, Personal, Research Grant, Medical writing support: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Other, Travel/accommodation/ expenses: F. Hoffmann-La Roche Ltd. V. López-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: F. Hoffmann-La Roche Ltd. J. Steinseifer: 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: 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 Inc.; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd; Non-Financial Interests, Personal, Research Grant, Medical writing support: F. Hoffmann-La Roche Ltd. G. Spera: Financial Interests, Personal, Full or part-time Employment, Senior Clinical Research Physician: Translational Research in Oncology; Non-Financial Interests, Personal, Research Grant, Medical writing support: 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: F. Hoffmann-La Roche Ltd. P.A. Fasching: Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Institutional, Research Grant: Biontech; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme; Financial Interests, Personal, Invited Speaker: Merck Sharp & Dohme; Financial Interests, Institutional, Research Grant: Cepheid; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Advisory Board: SeaGen; Financial Interests, Personal, Invited Speaker: SeaGen; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Advisory Board: Hexal; Financial Interests, Personal, Advisory Board: Agendia; Non-Financial Interests, Personal, Research Grant, Medical writing support: F. 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