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.
Notice bibliographique
Résumé
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.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,003 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,004 | 0,000 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».