211MO - Giredestrant (GDC-9545) vs physician choice of endocrine monotherapy (PCET) in patients (pts) with ER+, HER2– locally advanced/metastatic breast cancer (LA/mBC): Primary analysis of the phase II, randomised, open-label acelERA BC study

Background

ET is the mainstay management for ER+ BC; guidelines recommend ET before chemotherapy in LA/mBC. Giredestrant, a highly potent, non-steroidal, oral selective ER antagonist and degrader (SERD), achieves robust ER occupancy and was well tolerated and active as a single agent and in combination with palbociclib, regardless of ESR1 mutation, in phase I/II studies. acelERA BC (NCT04576455) compares giredestrant and PCET for ER+, HER2– LA/mBC in the 2^nd/3^rd line. We report the primary results.

Methods

Post- and pre-/peri-menopausal women, or men, ≥18 years with measurable disease or evaluable bone lesions, who progressed after 1–2 lines of systemic therapy (≤1 targeted, ≤1 chemotherapy regimen, prior fulvestrant allowed) were randomised 1:1 to giredestrant (30 mg PO QD) or fulvestrant/aromatase inhibitor per local guidelines (+LHRH agonist in pre-/peri-menopausal women, and men) until disease progression/unacceptable toxicity. Stratification was by visceral vs non-visceral disease, prior CDK4/6 inhibitor (yes/no) and prior fulvestrant (yes/no). The primary endpoint was investigator-assessed progression-free survival (INV-PFS).

Results

At cut-off (18/02/22), median follow-up was 7.89 months; 39% of pts had baseline ESR1 mutations; 71%/28% had 1/2 prior therapy lines. Efficacy/safety are shown in the table. Updated data with longer follow-up will be presented. Table: 211MO

Treatment effect was consistent across most key subgroups Overall survival was immature * In circulating tumour DNA ^† 2 ischemic strokes; 1 related which became fatal after cut-off ^‡ 1 pulmonary embolism AE, adverse event; CBR, clinical benefit rate; CI, confidence interval; HR, hazard ratio (stratified); ORR, objective response rate

Conclusions

While acelERA BC did not meet its primary endpoint of INV-PFS, giredestrant showed a numerical improvement vs PCET. A higher CBR and ORR was also observed in favour of giredestrant. In pts with higher dependence on ER activity, such as those with ESR1 mutations, the PFS benefit was more pronounced. Giredestrant was well tolerated, with a safety profile comparable to PCET and consistent with known ET risks. Giredestrant continues to be investigated in other studies.

Clinical trial identification

NCT04576455 (October 6, 2020).

Editorial acknowledgement

Support for third-party writing assistance for this abstract, furnished by Daniel Clyde, 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

M. Martin Jimenez: Financial Interests, Personal, Other, Consulting/advisory: F. Hoffmann-La Roche Ltd/ Genentech, Novartis, Pfizer, Lilly, AstraZeneca, Daiichi Sankyo; Financial Interests, Personal, Speaker’s Bureau: Lilly/ImClone, Roche/Genentech, Pierre Fabre; Financial Interests, Personal, Other, Honoraria: Roche/Genentech, Lilly, Pfizer, Novartis, Pierre Fabre, Seattle Genetics ; Financial Interests, Institutional, Funding: Novartis, Roche, PUMA Biotechnology; Non-Financial Interests, Personal, Funding, Medical writing support: F. Hoffmann-La Roche Ltd. E. Lim: Financial Interests, Personal, Other, Consulting/advisory: Lilly, Novartis, Pfizer, Roche; Financial Interests, Institutional, Funding: Novartis, Roche; Financial Interests, Personal, Other, Patents/royalties/IP: Sensitization of BCL-2-expressing breast tumors to chemotherapy by the BH3 mimetic ABT-737: Walter & Eliza Hall Institute of Medical Research; Financial Interests, Personal, Other, Travel/accommodation/expenses: Lilly; Non-Financial Interests, Personal, Funding, Medical writing support: F. Hoffmann-La Roche Ltd. M. Chavez Mac Gregor: Financial Interests, Personal, Full or part-time Employment: MD Anderson Physician's Network; Financial Interests, Personal, Other, Consulting/advisory: Roche/Genentech, Novartis, Pfizer, Asofarma, Roche/Genentech, Exact Sciences, AstraZeneca/ Daiichi Sankyo, AstraZeneca; Financial Interests, Personal, Other, Travel/accommodation/expenses: Pfizer; Financial Interests, Personal, Expert Testimony: Abbott Laboratories, Pfizer; Financial Interests, Personal, Other, Honoraria: Pfizer, Eisai; Financial Interests, Institutional, Funding: Novartis, Genentech/Roche, Pfizer; Non-Financial Interests, Personal, Member of the Board of Directors, Volunteer-Member, Board of Directors: Legacy Healthcare Services, The Hope Foundation ; Non-Financial Interests, Personal, Funding, Medical writing support: F. Hoffmann-La Roche Ltd. A. Bardia: Financial Interests, Personal, Other, Consulting/advisory: Novartis, Genentech, Pfizer, Spectrum Pharmaceuticals, BioTheranostics, Merck, Radius Health, Immunomedics, Sanofi, Puma Biotechnology, Daiichi Sankyo/AstraZeneca, Foundation Medicine, Philips ; Financial Interests, Institutional, Other, Consulting/advisory: Immunomedics, Novartis, Genentech/Roche, Pfizer, Radius Health, Innocrin Pharma; Financial Interests, Institutional, Funding: Genentech, Novartis, Pfizer, Merck, Sanofi, Radius Health, Immunomedics, AstraZeneca/Daiichi Sankyo; Non-Financial Interests, Personal, Funding, Medical writing support: F. Hoffmann-La Roche Ltd. J. Wu: Financial Interests, Institutional, Funding: National Natural ScienceFoundation, Roche; Financial Interests, Personal, Other, Honoraria: Lilly, Roche, AstraZeneca, Pfizer; Financial Interests, Personal, Proprietary Information, Microvascular anastomosis support dilator; degradable breast-conserving stent: Fudan University Shanghai Cancer Center; Non-Financial Interests, Personal, Leadership Role, Chairman: Chinese Breast Cancer Society; Non-Financial Interests, Personal, Leadership Role, Vice chairman: Breast Surgeon Committee; Non-Financial Interests, Personal, Leadership Role: Chinese College of Surgeons; Non-Financial Interests, Personal, Funding, Medical writing support: F. Hoffmann-La Roche Ltd. Q. Zhang: Financial Interests, Institutional, Funding: Roche; Non-Financial Interests, Personal, Funding, Medical writing support: F. Hoffmann-La Roche Ltd. Z. Nowecki: Financial Interests, Personal, Other, Travel/accommodation/expenses: F. Hoffmann-La Roche Ltd/ Genentech; Financial Interests, Institutional, Funding: F. Hoffmann-La Roche Ltd; Non-Financial Interests, Personal, Funding, Medical writing support: F. Hoffmann-La Roche Ltd. F. Cruz: Financial Interests, Institutional, Funding: Roche; Non-Financial Interests, Personal, Funding, Medical writing support: F. Hoffmann-La Roche Ltd. R. Safin: Financial Interests, Personal, Speaker’s Bureau: F. Hoffmann-La Roche Ltd; Financial Interests, Institutional, Funding: F. Hoffmann-La Roche Ltd; Non-Financial Interests, Personal, Funding, Medical writing support: F. Hoffmann-La Roche Ltd. S. Kim: Financial Interests, Institutional, Other, Consulting/advisory: Lilly; Financial Interests, Personal, Other, Consulting/advisory: Novartis, AstraZeneca, Dae Hwa Pharmaceutical Co, Ltd, ISU Abxis, Daiichi Sankyo; Financial Interests, Personal, Other, Honoraria: Novartis, AstraZeneca, Lilly; Financial Interests, Institutional, Funding: Novartis, Dongkook Pharm Co, Sanofi-Aventis, Roche; Financial Interests, Personal, Other, Consulting/advisory: Data safety monitoring/advisory board: Novartis, AstraZeneca, Lilly, Daiichi Sankyo; Non-Financial Interests, Personal, Leadership Role, Co-Chair: ESMO Breast 2021-2022; Financial Interests, Personal, Stocks/Shares: Genopeaks, Neogene TC; Non-Financial Interests, Personal, Funding, Medical writing support: F. Hoffmann-La Roche Ltd. C. Schem: Financial Interests, Institutional, Funding: Roche; Non-Financial Interests, Personal, Funding, Medical writing support: F. Hoffmann-La Roche Ltd. A. Montero: Financial Interests, Personal, Other, Consulting/advisory: New Century Health, Welwaze; Financial Interests, Personal, Other, Honoraria: Celgene, AstraZeneca, OncoSec; Financial Interests, Institutional, Funding: F. Hoffmann-La Roche Ltd; Non-Financial Interests, Personal, Funding, Medical writing support: F. Hoffmann-La Roche Ltd. S. Khan: Financial Interests, Personal, Other, Honoraria: Novartis; Financial Interests, Institutional, Funding: Roche; Financial Interests, Personal, Other, Travel/accommodation/expenses: Novartis; Non-Financial Interests, Personal, Funding, Medical writing support: F. Hoffmann-La Roche Ltd. R. Bandyopadhyay: Financial Interests, Personal, Full or part-time Employment: Genentech, Inc.; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd; Non-Financial Interests, Personal, Funding, Medical writing support: F. Hoffmann-La Roche Ltd. M. Shivhare: Financial Interests, Personal, Full or part-time Employment: Roche Products Limited; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd; Non-Financial Interests, Personal, Funding, Medical writing support: F. Hoffmann-La Roche Ltd. M. Patre: 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, Funding, Medical writing support: F. Hoffmann-La Roche Ltd. J. Martinalbo: 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, Funding, Medical writing support: F. Hoffmann-La Roche Ltd. L. Roncoroni: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd; Non-Financial Interests, Personal, Funding, Medical writing support: 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, Funding, Medical writing support: F. Hoffmann-La Roche Ltd. J. Sohn: Financial Interests, Institutional, Funding: Roche, MSD, AstraZeneca, Lilly, Pfizer, GSK, Daiichi Sankyo, Sanofi, Boehringer Ingelheim; Non-Financial Interests, Personal, Funding, Medical writing support: F. Hoffmann-La Roche Ltd.