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lidERA Breast Cancer (BC): Phase III adjuvant study of giredestrant vs. physician’s choice of endocrine therapy (PCET) in patients (pts) with estrogen receptor-positive, HER2-negative early BC (ER+, HER2– eBC).

2023· article· en· W4379284089 on OpenAlexaboutno aff
Charles E. Geyer, Aditya Bardia, Nadia Harbeck, Mothaffar F. Rimawi, Sara A. Hurvitz, Miguel Martín, Sherene Loi, Shigehira Saji, Kyung Hae Jung, Gustavo Werutsky, Daniil Stroyakovskiy, Vanesa López-Valverde, Michael Davis, Tanja Badovinac Črnjević, Pablo Perez-Moreno, Peter Schmid

Bibliographic record

VenueJournal of Clinical Oncology · 2023
Typearticle
Languageen
FieldMedicine
TopicAdvanced Breast Cancer Therapies
Canadian institutionsnot available
FundersF. Hoffmann-La Roche
KeywordsMedicineLetrozoleTamoxifenInternal medicineAnastrozoleOncologyExemestaneFulvestrantBreast cancerTolerabilityEstrogen receptorHazard ratioAdverse effectCancerGynecologyConfidence interval

Abstract

fetched live from OpenAlex

TPS616 Background: Despite best management with standard ETs, ≤ 20% of pts with ER+, HER2– eBC develop resistance (due to ESR1 mutations that can drive estrogen-independent transcription and proliferation) and have high recurrence rates. New treatments are needed to reduce recurrence risk and improve survival, tolerability, quality of life, and adherence. Giredestrant, a highly potent, nonsteroidal oral selective ER antagonist and degrader, achieves robust ER occupancy and is active against ER-sensitive or ESR1-mutated tumors. It is more potent in vitro and achieves higher ER occupancy in vivo than fulvestrant. Early-phase studies showed that 30 mg daily as a single agent has promising clinical and pharmacodynamic activity and is well tolerated for ER+, HER2– BC. Methods: lidERA BC (NCT04961996) is a Phase III, global, randomized, open-label, multicenter study evaluating adjuvant giredestrant vs. PCET in ER+, HER2– eBC. Pts are randomized 1:1 to oral 30 mg daily giredestrant or PCET (tamoxifen, anastrozole, letrozole, or exemestane; per prescribing information). Stratification factors: 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); menopausal status (pre-/peri- vs. postmenopausal). Pts will be treated for ≥ 5 years. Continuing PCET > 5 years is per investigator discretion and local standard of care. Eligibility: Female/male; medium-/high-risk stage I–III ER+, HER2– eBC; prior curative surgery; completion of (neo)adjuvant chemotherapy (if given) and/or surgery < 12 months before enrollment; no prior ET (≤ 12 weeks of [neo]adjuvant ET allowed). For men and pre-/perimenopausal women, an LHRH agonist will be given per local prescribing information (mandatory for the giredestrant arm). Primary endpoint: Invasive disease-free survival (IDFS, excluding second non-primary BC). 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. This study also aims to improve health equity in research and expand clinical trial access. It will use/develop digital healthcare solutions, enabling better understanding of pts’ needs and adherence to ET. The primary endpoint analysis will use a stratified log-rank test at an overall 0.05 significance level (two-sided). Interim and futility analyses are planned; an independent data monitoring committee will be in place. 2950/4100 pts have been recruited globally. Clinical trial information: NCT04961996 .

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.365
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0030.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.059
GPT teacher head0.439
Teacher spread0.380 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations11
Published2023
Admission routes1
Has abstractyes

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