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Background: The primary aim of the NRG Oncology/NSABP B-52 clinical trial was to test if estrogen deprivation (ED) administered concomitantly with neoadjuvant docetaxel, carboplatin, trastuzumab, and pertuzumab (TCHP), would improve the pCR rate in patients with HER2+/ER+ early breast cancer. A numerical increase in the pCR rate was observed with ED (46.1% v 40.9%), but the difference was not statistically significant. The purposes of this study were to assess the association of sTILs in pretreatment biopsies with pCR in the total population and within the molecular subtypes of breast cancer and to assess changes in sTILs between pre- and on-treatment biopsies. The secondary endpoints of recurrence-free interval (RFI) and overall survival (OS) are currently being analyzed and will be presented along with association of these endpoints with sTILs in pretreatment biopsies in the total cohort and within molecular subtypes. Methods: Scoring of sTILs on routine H&E slides from pre-treatment biopsies with sufficient tumor from 249 of the 315 patients (79%) entered in B-52 were performed by one of two pathologists (SKM, RSM). Both pathologists scored sTILs on a subset of 64 patients to document concordance. Wilcoxon two-sided test, box and whisker plots, and forest plots were used to assess associations with pCR. Molecular subtypes were determined utilizing RNA-seq data and AIMS subtyping method. On-treatment biopsies were available in 46 patients and were scored and compared to paired baseline samples. Results: Good concordance between pathologists was established with an inter-pathologist difference of ˂20% difference between scores in 92% of cases. sTILs in pre-treatment samples were associated with pCR across both arms of the trial (p=0.0074) and in the TCHP+ED arm (p=0.033), but not in the TCHP arm (p=0.093). The distribution of intrinsic subtypes was 34% luminal B, 29% luminal A, 28% HER2E, 5.8% normal, and 2.7% basal, with no significant differences between the arms. Presence of sTILs showed a trend for association with pCR in HER2E pre-treatment samples (p=0.054) but not in non-HER2E (p=0.75). Similarly, sTILs were associated with pCR in non-luminal tumors (p=0.055) but not in luminal tumors (p=0.44). Stratification by treatment arm and menopausal status suggested sTILs are associated with pCR in premenopausal women treated with TCHP (OR: 1.04, 95% CI=1.00-1.09). Interestingly, decreases in the sTIL scores with treatment were associated with pCR in the TCHP+ED arm (p=0.01) but not in the TCHP arm. Analysis of RFI and OS on B-52 is ongoing and will be presented along with associations of sTILs with intrinsic subtypes for RFI and OS. Conclusions: Although a positive correlation between sTILs and pCR was observed, the clinical utility appears limited because of the extensive overlap in the TIL scores between pCR and non-pCR tumors. Significance for a positive association of sTILs with pCR was detected in HER2E but not in luminal tumors. This may be due to the molecular differences of the subtypes, or the make-up of the TILs, or both. The association of a decrease in sTILs with TCHP+ED treatment needs further investigation. The small number of samples is a limitation of the study; however, the B-52 protocol specified that the collection of the B-52 samples was for the purpose of exploratory analysis. Our results highlight the molecular heterogeneity of the HER+/ER+ patient population and suggests that different treatment strategies may be required in future treatment regimens for this patient population. Support: NSABP Foundation; BCRF; 3U10CA180868-03S2, -180822; UG1CA189867; Genentech. Citation Format: Katherine L. Pogue-Geile, Sai K. Maley, Rim S. Kim, Ying Wang, Roberto Salgado, Corey Lipchik, Huichen Feng, Reena S. Cecchini, Samuel A. Jacobs, Ashok Srinivasan, Eleftherios (Terry) Mamounas, Charles E. Geyer Jr, Priya Rastogi, C. Kent Osborne, Soonmyung Paik, Norman Wolmark, Peter C. Lucas, Mothaffar Rimawi. Association of stromal tumor infiltrating lymphocytes (sTILs) in pretreatment biopsies in different molecular subtypes of HER2+/ER+ breast cancer: Assessment of NRG Oncology/NSABP B-52 [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-04-10.

Background: The CLEOPATRA trial established trastuzumab, pertuzumab and a taxane (THP) as a standard of care for first line metastatic, HER2-positve breast cancer with median progression-free survival (PFS) of 18.7 months and median OS of 57 months. NRG BR004 was a phase III, placebo-controlled trial designed to determine whether the addition of the PD-L1 inhibitor, atezolizumab, to THP would improve progression-free survival (PFS), relative to THP/placebo in patients with newly documented HER2-positive measurable metastatic breast cancer. Methods: BR004 was designed to detect an improvement in the primary endpoint of PFS in patients with measurable disease from 16.5 to 22.5 months with addition of atezolizumab (HR 0.733). A sample size of 600 would provide 80% power with a type I error rate of 0.05 to detect such an improvement when 326 PFS events had been reported. Monthly accrual was projected at 30 patients per month with completion of accrual in 24 months. In addition to routine monitoring of safety data by the IDMC every 6 months, a formal analysis of the toxicity data was to be performed 16 weeks after the 100th patient had been randomized with review by the IDMC. Results: First patient was randomized on May 1, 2019, and after 37 months 190 patients had been randomized. Several amendments were not successful in addressing the low accrual rate. The IDMC began regular monitoring of safety and accrual data in July 2020 and reviewed the formal safety analysis in February 2022. As of the February 2022 IDMC meeting, four Grade 5 adverse events (AEs) had been reported (2 occurring in 2020 and 2 in 2021), one of which occurred in a patient with evolving liver failure due to rapid disease progression at the start of therapy. The recommendation was to continue without modification, but notice was given the Grade 5 AEs had occurred on the same treatment arm without unblinding. When additional Grade 5 AEs occurred on 3/4/2022 and 4/27/2022 both on the same study arm with none reported on the other arm, accrual was held until the IDMC could review updated safety data, narratives of the Grade 5 AEs and the overall context of the trial. There was no evidence of clinically important imbalances between Grade 3 and Grade 4 AEs between the arms., Based on an uncertain but material safety signal, the ongoing accrual challenges, and determination that the clinical question being addressed was no longer sufficiently compelling, the IDMC recommended that the trial should be permanently closed to further enrollment. Summary safety data from 187 treated patients are provided in the Table. A decision was made to discontinue atezolizumab/placebo in patients receiving the investigational component of the trial therapy and unblind investigators and patients. The study will continue to collect information on PFS events, deaths and late immune AEs through April of 2024 when PFS and OS will be analyzed. Conclusions: The imbalance in Grade 5 AEs which occurred on BR004 coupled with continued poor accrual and the changing landscape in HER2+ MBC resulted in early closure of enrollment and unblinding of patients. Follow-up continues to assess PFS, OS and monitor for delayed immune AEs. Support: U10CA180868, -189867, -180822; U24CA196067; and Genentech. Citation Format: Charles E. Geyer, Jr, Gong Tang, Priya Rastogi, Vicente Valero, Stephen K. Chia, Erin F. Cobain, Elias Obeid, David B. Page, Andrew S. Poklepovic, William J. Irvin, Jr., Adam M. Brufsky, Irene L. Wapnir, Jennifer M. Suga, Eleftherios (Terry) Mamounas, Norman Wolmark. Safety Analyses of NRG BR004: A Randomized, Double-blind, Phase III Trial of Taxane/Trastuzumab/Pertuzumab with Atezolizumab or Placebo in First-line HER2-Positive Metastatic Breast Cancer (MBC) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT2-16-05.

BACKGROUND Endocrine therapies (ETs) that target estrogen receptor (ER) activity and/or estrogen synthesis are the mainstay of ER+ breast cancer (BC) treatment. Despite best management, ≤20% of patients (pts) with ER+/HER2– early BC (eBC) develop resistance (in some cases due to 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, a highly potent, nonsteroidal oral selective ER antagonist and degrader (SERD), achieves robust ER occupancy and is active against tumors that retain ER-sensitivity or have ESR1 mutation(s). It 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 efficacy and safety of adjuvant giredestrant vs physician’s choice of adjuvant ET (PCET) 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 PCET (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 PCET for ≥5 years. Continuing PCET 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 < 12 months prior to enrollment; no prior ET (≤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 pts’ 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 1018/4100 pts have been recruited globally. 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. AB, PS and CG contributed equally. This abstract was originally presented at SABCS 2021 (OT2-11-09). a>Disclosure(s): Peter Schmid, MD, PhD: Astellas Pharma: Contracted Research (Ongoing); AstraZeneca: Consulting Fees (e.g., advisory boards) (Ongoing), Contracted Research (Ongoing), Honoraria (Ongoing); Bayer: Consulting Fees (e.g., advisory boards) (Ongoing), Honoraria (Ongoing); Boehringer Ingelheim: Consulting Fees (e.g., advisory boards) (Ongoing), Honoraria (Ongoing); Celgene: Consulting Fees (e.g., advisory boards) (Ongoing); Eisai: Consulting Fees (e.g., advisory boards) (Ongoing); F. Hoffmann-La Roche Ltd.: Third-party writing assistance for this abstract, furnished by Sunaina Indermun, BPharm, PhD, of Health Interactions, was provided by Roche (Ongoing); Genentech: Contracted Research (Ongoing); Medivation Inc.: Contracted Research (Ongoing); Merck: Consulting Fees (e.g., advisory boards) (Ongoing), Honoraria (Ongoing); Novartis: Consulting Fees (e.g., advisory boards) (Ongoing), Contracted Research (Ongoing), Honoraria (Ongoing); OncoGenex: Contracted Research (Ongoing); Pfizer: Consulting Fees (e.g., advisory boards) (Ongoing), Honoraria (Ongoing); Puma Biotechnology: Consulting Fees (e.g., advisory boards) (Ongoing), Honoraria (Ongoing); Roche: Consulting Fees (e.g., advisory boards) (Ongoing), Contracted Research (Ongoing), Honoraria (Ongoing) Charles E. Geyer Jr, MD, FACP: Abbvie: Contracted Research (Terminated, July 1, 2022), Writing assistance (Terminated, July 1, 2022); AstraZeneca: Contracted Research (Ongoing), Writing assistance (Ongoing); Daiichi/Sankyo: Contracted Research (Ongoing); Exact Sciences: Consulting Fees (e.g., advisory boards) (Ongoing); F. Hoffman-La Roche Ltd: Contracted Research (Ongoing), Third-party writing assistance for this abstract, furnished by Sunaina Indermun, BPharm, PhD, of Health Interactions, was provided by Roche) (Ongoing); Genentech: Contracted Research (Ongoing), Writing assistance (Ongoing) Nadia Harbeck, MD, PhD: Amgen: Fees for Non-CME Services Received Directly from Commercial Interest or their Agents (e.g., speakers’ bureaus) (Ongoing); AstraZeneca: Consulting Fees (e.g., advisory boards) (Ongoing), Fees for Non-CME Services Received Directly from Commercial Interest or their Agents (e.g., speakers’ bureaus) (Ongoing); Daiichi Sankyo: Consulting Fees (e.g., advisory boards) (Ongoing), Fees for Non-CME Services Received Directly from Commercial Interest or their Agents (e.g., speakers’ bureaus) (Ongoing); Eli Lilly: Consulting Fees (e.g., advisory boards) (Ongoing), Fees for Non-CME Services Received Directly from Commercial Interest or their Agents (e.g., speakers’ bureaus) (Ongoing); Exact Sciences: Fees for Non-CME Services Received Directly from Commercial Interest or their Agents (e.g., speakers’ bureaus) (Ongoing); MSD: Consulting Fees (e.g., advisory boards) (Ongoing), Fees for Non-CME Services Received Directly from Commercial Interest or their Agents (e.g., speakers’ bureaus) (Ongoing); Novartis: Consulting Fees (e.g., advisory boards) (Ongoing), Fees for Non-CME Services Received Directly from Commercial Interest or their Agents (e.g., speakers’ bureaus) (Ongoing); Pfizer: Consulting Fees (e.g., advisory boards) (Ongoing), Fees for Non-CME Services Received Directly from Commercial Interest or their Agents (e.g., speakers’ bureaus) (Ongoing); Pierre Fabre: Consulting Fees (e.g., advisory boards) (Ongoing), Fees for Non-CME Services Received Directly from Commercial Interest or their Agents (e.g., speakers’ bureaus) (Ongoing); Roche: Consulting Fees (e.g., advisory boards) (Ongoing), Contracted Research (Ongoing), Fees for Non-CME Services Received Directly from Commercial Interest or their Agents (e.g., speakers’ bureaus) (Ongoing), Third-party writing assistance for this abstract, furnished by Sunaina Indermun, BPharm, PhD, of Health Interactions, was provided by Roche (Ongoing); Sandoz: Consulting Fees (e.g., advisory boards) (Ongoing); Seagen: Consulting Fees (e.g., advisory boards) (Ongoing), Fees for Non-CME Services Received Directly from Commercial Interest or their Agents (e.g., speakers’ bureaus) (Ongoing); WSG: Ownership Interest (stocks, stock options, patent or other intellectual property or other ownership interest excluding diversified mutual funds) (Ongoing) Mothaffar Rimawi, MD: Daiichi Sankyo: Fees for Non-CME Services Received Directly from Commercial Interest or their Agents (e.g., speakers’ bureaus) (Ongoing); F. Hoffmann-La Roche Ltd.: Contracted Research (Ongoing), Third-party writing assistance for this abstract, furnished by Sunaina Indermun, BPharm, PhD, of Health Interactions, was provided by Roche (Ongoing); Genentech: Fees for Non-CME Services Received Directly from Commercial Interest or their Agents (e.g., speakers’ bureaus) (Ongoing); Macrogenics: Fees for Non-CME Services Received Directly from Commercial Interest or their Agents (e.g., speakers’ bureaus) (Ongoing); Pfizer: Contracted Research (Ongoing); Seattle Genetics: Fees for Non-CME Services Received Directly from Commercial Interest or their Agents (e.g., speakers’ bureaus) (Ongoing) Sara Hurvitz, MD, FACP: Ambrx: Contracted Research (Ongoing); Amgen: Contracted Research (Ongoing); Arvinas: Contracted Research (Ongoing); Astra Zeneca: Contracted Research (Ongoing); Bayer: Contracted Research (Ongoing); Cytomx: Contracted Research (Ongoing); Daiichi-Sankyo: Contracted Research (Ongoing); Dignitana: Contracted Research (Ongoing); Eli Lilly: Contracted Research (Ongoing); Genentech/Roche: Contracted Research (Ongoing); Gilead: Contracted Research (Ongoing); GSK: Contracted Research (Ongoing); Ideal Implant: Ownership Interest (stocks, stock options, patent or other intellectual property or other ownership interest excluding diversified mutual funds) (Ongoing); Immunomedics: Contracted Research (Ongoing); Macrogenics: Contracted Research (Ongoing); Novartis: Contracted Research (Ongoing); OBI Pharma: Contracted Research (Ongoing); Orinove: Contracted Research (Ongoing); Pfizer: Contracted Research (Ongoing); Phoenix Molecular Designs, Ltd.: Contracted Research (Ongoing); Pieris: Contracted Research (Ongoing); PUMA: Contracted Research (Ongoing); Radius: Contracted Research (Ongoing); Sanofi: Contracted Research (Ongoing); Seattle Genetics/Seagen: Contracted Research (Ongoing); Zymeworks: Contracted Research (Ongoing) Miguel Martín, MD, PhD: AstraZeneca: Consulting Fees (e.g., advisory boards) (Ongoing), Fees for Non-CME Services Received Directly from Commercial Interest or their Agents (e.g., speakers’ bureaus) (Ongoing); Daiichi Sankyo: Consulting Fees (e.g., advisory boards) (Ongoing), Fees for Non-CME Services Received Directly from Commercial Interest or their Agents (e.g., speakers’ bureaus) (Ongoing); F. Hoffmann-La Roche: Third-party writing assistance for this abstract, furnished by Eleanor Porteous, MSc, of Health Interactions, was provided by Roche (Ongoing); Genentech/Roche: Consulting Fees (e.g., advisory boards) (Ongoing), Contracted Research (Ongoing), Fees for Non-CME Services Received Directly from Commercial Interest or their Agents (e.g., speakers’ bureaus) (Ongoing), Third-party writing assistance for this abstract, furnished by Sunaina Indermun, BPharm, PhD, of Health Interactions, was provided by Roche (Ongoing); Gilead: Consulting Fees (e.g., advisory boards) (Ongoing), Fees for Non-CME Services Received Directly from Commercial Interest or their Agents (e.g., speakers’ bureaus) (Ongoing); Lilly/ImClone: Consulting Fees (e.g., advisory boards) (Ongoing), Fees for Non-CME Services Received Directly from Commercial Interest or their Agents (e.g., speakers’ bureaus) (Ongoing), Honoraria (Ongoing); Novartis: Consulting Fees (e.g., advisory boards) (Ongoing), Contracted Research (Ongoing), Fees for Non-CME Services Received Directly from Commercial Interest or their Agents (e.g., speakers’ bureaus) (Ongoing), Honoraria (Ongoing); Pfizer: Consulting Fees (e.g., advisory boards) (Ongoing), Fees for Non-CME Services Received Directly from Commercial Interest or their Agents (e.g., speakers’ bureaus) (Ongoing), Honoraria (Ongoing); Pierre Fabre: Fees for Non-CME Services Received Directly from Commercial Interest or their Agents (e.g., speakers’ bureaus) (Ongoing), Honoraria (Ongoing); Seagen: Consulting Fees (e.g., advisory boards) (Ongoing), Fees for Non-CME Services Received Directly from Commercial Interest or their Agents (e.g., speakers’ bureaus) (Ongoing), Honoraria (Ongoing) Sherene Loi, MBBS (Hons), PhD, FRACP, FAHMS, GAICD: Aduro Biotech, Inc.: Consulting Fees (e.g., advisory boards) (Ongoing); Akamara Therapeutics: Uncompensated scientific advisory board member (Ongoing); AstraZeneca: Consulting Fees (e.g., advisory boards) (Ongoing), Uncompensated consultant (Ongoing); BMS: Uncompensated consultant (Ongoing); Breast Cancer Research Foundation, New York: Supported by the Breast Cancer Research Foundation, New York (Ongoing); G1 Therapeutics: Consulting Fees (e.g., advisory boards) (Ongoing); GlaxoSmithKline: Consulting Fees (e.g., advisory boards) (Ongoing); Merck: Uncompensated consultant (Ongoing); National Breast Cancer Foundation of Australia Endowed Chair: Supported by the National Breast Cancer Foundation of Australia Endowed Chair (Ongoing); Novartis: Consulting Fees (e.g., advisory boards) (Ongoing), Uncompensated consultant (Ongoing); Roche-Genentech: Consulting Fees (e.g., advisory boards) (Ongoing), Contracted Research (Ongoing), Third-party writing assistance for this abstract, furnished by Sunaina Indermun, BPharm, PhD, of Health Interactions, was provided by Roche (Ongoing), Uncompensated consultant (Ongoing); Seattle Genetics: Uncompensated consultant (Ongoing); Silverback Therapeutics: Consulting Fees (e.g., advisory boards) (Ongoing) Shigehira Saji, MD, PhD: Astra Zeneca: Consulting Fees (e.g., advisory boards) (Ongoing), Contracted Research (Ongoing), Fees for Non-CME Services Received Directly from Commercial Interest or their Agents (e.g., speakers’ bureaus) (Ongoing); Bayer: Fees for Non-CME Services Received Directly from Commercial Interest or their Agents (e.g., speakers’ bureaus) (Ongoing); Boerhringer-ingelheim: Fees for Non-CME Services Received Directly from Commercial Interest or their Agents (e.g., speakers’ bureaus) (Ongoing); Breast International Group: Executive board member (Ongoing); Chugai: Consulting Fees (e.g., advisory boards) (Ongoing), Contracted Research (Ongoing), Fees for Non-CME Services Received Directly from Commercial Interest or their Agents (e.g., speakers’ bureaus) (Ongoing); Daiichi Sankyo: Consulting Fees (e.g., advisory boards) (Ongoing), Contracted Research (Ongoing), Fees for Non-CME Services Received Directly from Commercial Interest or their Agents (e.g., speakers’ bureaus) (Ongoing); Eisai: Fees for Non-CME Services Received Directly from Commercial Interest or their Agents (e.g., speakers’ bureaus) (Ongoing); Eli Lilly: Consulting Fees (e.g., advisory boards) (Ongoing), Contracted Research (Ongoing), Fees for Non-CME Services Received Directly from Commercial Interest or their Agents (e.g., speakers’ bureaus) (Ongoing); F. Hoffmann-La Roche Ltd.: Contracted Research (Ongoing), Third-party writing assistance for this abstract, furnished by Sunaina Indermun, BPharm, PhD, of Health Interactions, was provided by Roche (Ongoing); Japan Breast Cancer Research Group: Executive board member (Ongoing); Japanese Breast Cancer Society: Executive board member (Ongoing); Japanese Society of Medical Oncology: Executive board member (Ongoing); Kyowa Kirin: Consulting Fees (e.g., advisory boards) (Ongoing), Fees for Non-CME Services Received Directly from Commercial Interest or their Agents (e.g., speakers’ bureaus) (Ongoing); MSD: Consulting Fees (e.g., advisory boards) (Ongoing), Contracted Research (Ongoing), Fees for Non-CME Services Received Directly from Commercial Interest or their Agents (e.g., speakers’ bureaus) (Ongoing); Nihonkayaku: Fees for Non-CME Services Received Directly from Commercial Interest or their Agents (e.g., speakers’ bureaus) (Ongoing); Novartis: Fees for Non-CME Services Received Directly from Commercial Interest or their Agents (e.g., speakers’ bureaus) (Ongoing); Ono: Consulting Fees (e.g., advisory boards) (Ongoing), Fees for Non-CME Services Received Directly from Commercial Interest or their Agents (e.g., speakers’ bureaus) (Ongoing); Pfizer: Consulting Fees (e.g., advisory boards) (Ongoing), Fees for Non-CME Services Received Directly from Commercial Interest or their Agents (e.g., speakers’ bureaus) (Ongoing); Taiho: Contracted Research (Ongoing), Fees for Non-CME Services Received Directly from Commercial Interest or their Agents (e.g., speakers’ bureaus) (Ongoing); Takeda: Fees for Non-CME Services Received Directly from Commercial Interest or their Agents (e.g., speakers’ bureaus) (Ongoing) Kyung Hae Jung, MD, MS, PhD: AstraZeneca: Consulting Fees (e.g., advisory boards) (Ongoing); Celgene: Consulting Fees (e.g., advisory boards) (Ongoing); Daiichi-Sankyo: Consulting Fees (e.g., advisory boards) (Ongoing); Eisai: Consulting Fees (e.g., advisory boards) (Ongoing); Everest Medicine: Consulting Fees (e.g., advisory boards) (Ongoing); Merck: Consulting Fees (e.g., advisory boards) (Ongoing); MSD: Consulting Fees (e.g., advisory boards) (Ongoing); Novartis: Consulting Fees (e.g., advisory boards) (Ongoing); Pfizer: Consulting Fees (e.g., advisory boards) (Ongoing); Roche: Consulting Fees (e.g., advisory boards) (Ongoing), Contracted Research (Ongoing), Third-party writing assistance for this abstract, furnished by Sunaina Indermun, BPharm, PhD, of Health Interactions, was provided by Roche (Ongoing); Takeda: Consulting Fees (e.g., advisory boards) (Ongoing) Gustavo Werutsky, MD, PhD: AstraZeneca: Consulting Fees (e.g., advisory boards) (Ongoing), Contracted Research (Ongoing), Honoraria (Ongoing); Bayer: Contracted Research (Ongoing); Beigene: Contracted Research (Ongoing); Daiichi Sankyo: Consulting Fees (e.g., advisory boards) (Ongoing); Genentech/Roche: Consulting Fees (e.g., advisory boards) (Ongoing), Contracted Research (Ongoing), Fees for Non-CME Services Received Directly from Commercial Interest or their Agents (e.g., speakers’ bureaus) (Ongoing); GSK: Contracted Research (Ongoing); Lilly: Contracted Research (Ongoing), Honoraria (Ongoing); MSD: Honoraria (Ongoing); Novartis: Consulting Fees (e.g., advisory boards) (Ongoing), Contracted Research (Ongoing), Honoraria (Ongoing); Pfizer: Consulting Fees (e.g., advisory boards) (Ongoing), Contracted Research (Ongoing), Honoraria (Ongoing); Sanofi: Consulting Fees (e.g., advisory boards) (Ongoing), Contracted Research (Ongoing); Seattle Genetics: Contracted Research (Ongoing) Daniil L. Stroyakovsky, MD: Roche: Consulting Fees (e.g., advisory boards) (Ongoing), Contracted Research (Ongoing), Third-party writing assistance for this abstract, furnished by Sunaina Indermun, BPharm, PhD, of Health Interactions, was provided by Roche (Ongoing) Vanesa López-Valverde, PharmD, PhD: F. Hoffmann-La Roche Ltd.: Ownership Interest (stocks, stock options, patent or other intellectual property or other ownership interest excluding diversified mutual funds) (Ongoing), Salary (Ongoing), Third-party writing assistance for this abstract, furnished by Sunaina Indermun, BPharm, PhD, of Health Interactions, was provided by Roche (Ongoing) Michael Davis, PsyD: F. Hoffmann-La Roche Ltd.: Ownership Interest (stocks, stock options, patent or other intellectual property or other ownership interest excluding diversified mutual funds) (Ongoing), Third-party writing assistance for this abstract, furnished by Sunaina Indermun, BPharm, PhD, of Health Interactions, was provided by Roche (Ongoing); Genentech, Inc.: Salary (Ongoing) Tanja Badovinac Crnjevic, MD, PhD: F. Hoffmann-La Roche Ltd.: Ownership Interest (stocks, stock options, patent or other intellectual property or other ownership interest excluding diversified mutual funds) (Ongoing), Salary (Ongoing), Third-party writing assistance for this abstract, furnished by Sunaina Indermun, BPharm, PhD, of Health Interactions, was provided by Roche (Ongoing) Pablo D. Perez-Moreno, MD: F. Hoffmann-La Roche Ltd.: Ownership Interest (stocks, stock options, patent or other intellectual property or other ownership interest excluding diversified mutual funds) (Ongoing), Third-party writing assistance for this abstract, furnished by Sunaina Indermun, BPharm, PhD, of Health Interactions, was provided by Roche (Ongoing); Genentech, Inc.: Salary (Ongoing) Aditya Bardia, MD, MPH: AstraZeneca: Consulting Fees (e.g., advisory boards) (Ongoing), Contracted Research (Ongoing); BioTheranostics: Consulting Fees (e.g., advisory boards) (Ongoing); Daiichi Sankyo: Consulting Fees (e.g., advisory boards) (Ongoing), Contracted Research (Ongoing); Eli Lilly: Consulting Fees (e.g., advisory boards) (Ongoing), Contracted Research (Ongoing); Foundation Medicine: Consulting Fees (e.g., advisory boards) (Ongoing); Genentech/Roche: Consulting Fees (e.g., advisory boards) (Ongoing), Contracted Research (Ongoing); Immunomedics/Gilead: Consulting Fees (e.g., advisory boards) (Ongoing), Contracted Research (Ongoing); Merck: Consulting Fees (e.g., advisory boards) (Ongoing), Contracted Research (Ongoing); Novartis: Consulting Fees (e.g., advisory boards) (Ongoing), Contracted Research (Ongoing); Pfizer: Consulting Fees (e.g., advisory boards) (Ongoing), Contracted Research (Ongoing); Phillips: Consulting Fees (e.g., advisory boards) (Ongoing); Radius Health: Consulting Fees (e.g., advisory boards) (Ongoing), Contracted Research (Ongoing); Sanofi: Consulting Fees (e.g., advisory boards) (Ongoing), Contracted Research (Ongoing) Citation Format: Peter Schmid, Charles E. Geyer Jr, Nadia Harbeck, Mothaffar Rimawi, Sara Hurvitz, Miguel Martín, Sherene Loi, Shigehira Saji, Kyung Hae Jung, Gustavo Werutsky, Daniil L. Stroyakovsky, Vanesa López-Valverde, Michael Davis, Tanja Badovinac Crnjevic, Pablo D. Perez-Moreno, Aditya Bardia. lidERA Breast Cancer: A phase III adjuvant study of giredestrant (GDC-9545) vs physician’s choice of endocrine therapy in patients with estrogen receptor+, HER2– early breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT2-03-02.