Abstract OT2-11-09: Lidera breast cancer: A phase III adjuvant study of giredestrant (GDC-9545) vs physician’s choice of endocrine therapy (ET) in patients (pts) with estrogen receptor-positive, HER2-negative early breast cancer (ER+/HER2- EBC)
Authors: Bardia Aditya , Schmid Peter , Harbeck Nadia , Rimawi Mothaffar F , Hurvitz Sara A , Loi Sherene , Saji Shigehira , Jung Kyung Hae , Werutsky Gustavo , Stroyakovskii Daniil , López-Valverde Vanesa , Tesarowski David , Ye Chenglin , Davis Michael , Crnjevic Tanja Badovinac , Perez-Moreno Pablo Diego , Geyer Charles E 
Published: March 2022

Abstract
BACKGROUND ETs that target ER activity and/or estrogen synthesis are the mainstay of ER+ BC treatment. Despite best management, up to 20% of pts with ER+/HER2- eBC develop resistance (in some cases due to the acquisition of tumor mutations in ESR1 that can drive estrogen-independent transcription and proliferation) and still have high recurrence rates on standard ETs. New treatment alternatives for ER+/HER2- eBC are needed to reduce risk of recurrence and improve survival, tolerability, quality of life, and adherence. Giredestrant is a highly potent, nonsteroidal oral selective ER antagonist and degrader (SERD). It achieves robust ER occupancy and is active against tumors that retain ER-sensitivity or have ESR1 mutation(s). Giredestrant has been demonstrated to be more potent in vitro and achieves higher ER occupancy in vivo than fulvestrant, the only currently approved SERD. Early phase clinical studies have demonstrated that single-agent giredestrant (30 mg daily) has promising clinical and pharmacodynamic activity, and is well-tolerated in the ER+/HER2- eBC and metastatic BC settings. TRIAL DESIGN This is a phase III, global, randomized, open-label, multicenter study evaluating the efficacy and safety of adjuvant giredestrant vs physician’s choice of adjuvant ET in pts with medium- and high-risk stage I-III histologically confirmed ER+/HER2- eBC. Pts are randomized 1:1 to oral 30 mg daily giredestrant or physician’s choice of standard ET (tamoxifen, anastrozole, letrozole, or exemestane, given according to prescribing information). Stratification factors are risk (medium vs high, based on anatomic [tumor size, nodal status] and biologic features [grade, Ki67, gene signatures if available]); geographic region (US/Canada/Western Europe vs Asia-Pacific vs rest of the world); prior chemotherapy (no vs yes); and menopausal status (pre-/perimenopausal vs postmenopausal). Beginning on Day 1 of Cycle 1, pts will be treated with giredestrant or physician’s choice of standard ET for at least 5 years. Continuing physician’s choice of standard ET after 5 years is at discretion of the investigator and per local standard of care. ELIGIBILITY Female/male pts with medium-/high-risk stage I-III ER+/HER2- eBC; prior curative surgery; completion of (neo)adjuvant chemotherapy (if administered) and/or surgery &lt;12 months prior to enrolment; no prior ET (up to 4 weeks of [neo]adjuvant ET is allowed). For men and pre-/perimenopausal women, a luteinizing hormone-releasing hormone agonist will be given per local prescribing information (mandatory for pts in the giredestrant arm). AIMS Primary endpoint: Invasive disease-free survival (IDFS). Secondary endpoints: Overall survival; IDFS (STEEP definition, including second non-primary BC); disease-free survival; distant recurrence-free survival; locoregional recurrence-free interval; safety; pharmacokinetics; pt-reported outcomes. In addition, this study aims to improve health equity in research and expand clinical trial access. The study will also use/develop digital healthcare solutions, which will enable better understanding of patients’ needs and their adherence to ET. STATISTICAL METHODS The primary endpoint analysis will use a stratified log-rank test at an overall 0.05 significance level (two-sided). An interim analysis and a futility analysis are planned, and an independent data monitoring committee will be in place. ACCRUAL Target enrollment is 4100 pts globally once the study is open for enrollment. CONTACT INFORMATION For more information or to refer a patient, email global.rochegenentechtrials@roche.com or call 1-888-662-6728 (USA only). Clinicaltrials.gov number NCT04961996.
Citation Format: Aditya Bardia, Peter Schmid, Nadia Harbeck, Mothaffar F Rimawi, Sara A Hurvitz, Sherene Loi, Shigehira Saji, Kyung Hae Jung, Gustavo Werutsky, Daniil Stroyakovskii, Vanesa López-Valverde, David Tesarowski, Chenglin Ye, Michael Davis, Tanja Badovinac Crnjevic, Pablo Diego Perez-Moreno, Charles E Geyer, Jr. Lidera breast cancer: A phase III adjuvant study of giredestrant (GDC-9545) vs physician’s choice of endocrine therapy (ET) in patients (pts) with estrogen receptor-positive, HER2-negative early breast cancer (ER+/HER2- EBC) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT2-11-09.