Camizestrant + CDK4/6 inhibitor (CDK4/6i) for the treatment of emergent <i>ESR1</i> mutations during first-line (1L) endocrine-based therapy (ET) and ahead of disease progression in patients (pts) with HR+/HER2– advanced breast cancer (ABC): Phase 3, double-blind ctDNA-guided SERENA-6 trial.
Notice bibliographique
Résumé
LBA4 Background: ESR1 mutations ( ESR1 m) constitutively activate the estrogen receptor (ER) and are the most common mechanism of acquired resistance to aromatase inhibitor (AI) + CDK4/6i. Molecular monitoring by ctDNA analysis can detect the emergence of ESR1 m during 1L AI + CDK4/6i. Camizestrant, the next-generation selective ER degrader (SERD) and complete ER antagonist, has shown anti-tumor activity in pts with and without detectable ESR1 m. SERENA-6 is the first global registrational Phase 3 trial assessing a ctDNA-guided approach to detect the emergence of ESR1 m during 1L AI + CDK4/6i to inform a switch in therapy ahead of disease progression. Methods: Pts with HR+/HER2– ABC who had received ≥6 months of 1L AI (anastrozole/letrozole) + CDK4/6i (abemaciclib/palbociclib/ribociclib) were enrolled and had ctDNA tested for ESR1 m every 2–3 months, coinciding with routine imaging. At ESR1 m detection, pts without evidence of disease progression were randomized 1:1 to switch to camizestrant (75 mg) with continued CDK4/6i (type and dose maintained) + placebo for AI vs continuing AI + CDK4/6i + placebo for camizestrant. The primary endpoint was investigator-assessed PFS (per RECIST v1.1). Prespecified interim analysis data cutoff was Nov 28, 2024. Results: 3,256 eligible pts were surveilled for ESR1 m using ctDNA until 315 eligible pts were randomized to switch to camizestrant (n=157) or continue with AI (n=158). All pts remained on the same CDK4/6i. ~50% of randomized pts had ESR1 m detected at the first ctDNA test. Baseline characteristics were well balanced between treatments. After 171 PFS events, hazard ratio for PFS was 0.44 (95% CI 0.31–0.60, p<0.00001; median PFS 16.0 vs 9.2 months). PFS benefit was consistent across subgroups. PFS rate at 12 months was 60.7% (95% CI 51.1–69.0) vs 33.4% (95% CI 24.9–42.2) and at 24 months was 29.7% (95% CI 19.0–41.2) vs 5.4% (95% CI 0.7–18.2). PFS2 hazard ratio was 0.52 (95% CI 0.33–0.81; 27% maturity). OS is immature (12%). Camizestrant + CDK4/6i was well tolerated with safety consistent with the known profiles of camizestrant, and of each CDK4/6i. Rates of treatment discontinuation due to adverse events were 1.3% for camizestrant and 1.9% for AI. Conclusions: Camizestrant + CDK4/6i guided by emergence of ESR1 m during 1L AI + CDK4/6i in pts with HR+/HER2– ABC resulted in a statistically significant and clinically meaningful improvement in PFS. SERENA-6 is the first global Phase 3 trial to demonstrate clinical utility of using ctDNA to detect and treat emerging resistance, ahead of disease progression. These findings represent a potential new treatment strategy to optimize and improve 1L patient outcomes. Clinical trial information: NCT04964934 .
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 machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,004 | 0,001 |
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 source (Gemma direct ou Codex distillé), 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 ».