Abstract 144P
Background
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.
Methods
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.
Results
This analysis included 201 Ki67-evaluable patients at BL and Week 2. Greater Ki67 reduction was observed with giredestrant vs A across AJCC stages, almost all tumour stages, in patients with N+ disease and regardless of ductal or lobular subtype (Table). Giredestrant treatment also resulted in a markedly larger Ki67 decrease vs A in PgR-negative tumours, a poor prognostic feature. As expected, a strong decrease in ER protein levels was observed after 2 weeks of treatment with giredestrant, with a trend for greater reduction in protein levels of PgR at Week 2 with giredestrant vs A. Data on gene expression changes in ER signalling will be presented. Table: 144P
| % Ki67 reduction | |||
| A | Giredestrant | ||
| AJCC stage | I | 66 | 75 |
| II | 68 | 75 | |
| III | 62 | 74 | |
| Primary tumour stage | T1 | 64 | 73 |
| T2 | 68 | 76 | |
| T3 | 65 | 80 | |
| T4 | 69 | 65 | |
| N status | cN0 | 59 | 72 |
| cN+ | 59 | 79 | |
| Histological grade | 1/2 | 67 | 76 |
| 3 | 66 | 68 | |
| Histological subtype | Ductal | 65 | 76 |
| Lobular | 68 | 71 | |
| PgR status | + | 70 | 77 |
| – | 39 | 60 |
Conclusions
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.
Clinical trial identification
NCT04436744 (June 18, 2020).
Editorial acknowledgement
Support 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 study
F. Hoffmann-La Roche Ltd.
Funding
F. Hoffmann-La Roche Ltd.
Disclosure
A. 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.