Neoadjuvant giredestrant (GDC-9545) plus palbociclib (P) versus anastrozole (A) plus P in postmenopausal women with estrogen receptor–positive, HER2-negative, untreated early breast cancer (ER+/HER2– eBC): Final analysis of the randomized, open-label, international phase 2 coopERA BC study.
Bibliographic record
Abstract
589 Background: Endocrine therapy (ET) is the therapeutic mainstay for ER+ BC. Giredestrant is a highly potent, nonsteroidal, oral, selective ER antagonist and degrader (SERD) which has demonstrated robust ER occupancy, is well tolerated, and has previously shown encouraging antitumor activity as monotherapy and in combination with P in metastatic BC. coopERA BC (NCT04436744) evaluated giredestrant in eBC and met its primary endpoint, highlighting superior Ki67 suppression with single-agent giredestrant vs A at Week 2. Giredestrant was well tolerated. Here, we report the final analysis. Methods: Eligible patients (pts) with measurable ER+/HER2– untreated eBC and baseline Ki67 score ≥5% (202 planned) were randomized 1:1 to receive, on Days 1–14 of a neoadjuvant window-of-opportunity phase, 30 mg oral daily (PO QD) giredestrant or 1 mg PO QD A followed by a 16-week neoadjuvant phase of QD giredestrant or A for four 28-day cycles with 125 mg PO P on Days 1–21. Randomization was stratified by tumor size, baseline Ki67 score, and progesterone receptor status. Endpoints assessed here included Ki67 suppression from baseline to surgery, complete cell cycle arrest (CCCA; Ki67 ≤2.7%) at surgery, objective response rate (ORR), and safety. Results: At final analysis (cutoff: Nov 24, 2021), 112 and 109 pts were randomized to the giredestrant and A arms, respectively (median age: 62 years each; stage I/IIa disease: 60% vs 54%). Consistent with the primary analysis, greater suppression of Ki67 was observed at surgery with giredestrant + P (–81% [95% confidence interval (CI): –86%, –75%]) vs A + P (–74% [95% CI: –80%, –67%]). Similarly, greater CCCA was achieved at surgery with giredestrant + P (20%) vs A + P (14%). ORR was similar between the two arms (giredestrant + P: 50% [95% CI: 40%, 60%]; A + P: 49% [95% CI: 39%, 59%]). ET-related adverse events (AEs) were non-serious and occurred at similar rates between the two arms. Related Grade ≥3 AE rates were also similar at 6% each. Interruption/withdrawal of ET due to AEs was low and similar for both arms. Conclusions: In this final analysis of coopERA BC, the greater suppression of Ki67 with giredestrant vs A observed at Week 2 in the primary analysis was maintained at surgery, and safety data remained consistent with the known safety profile of giredestrant. coopERA BC is the first randomized study to show superior antiproliferative activity of an oral SERD (giredestrant) over an aromatase inhibitor (A) in ER+/HER2– eBC; studies are ongoing to further assess giredestrant’s clinical benefit. Clinical trial information: NCT04436744.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.006 | 0.001 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".