Three-year disease-free survival in randomized trials of chemotherapy and HER2-targeted therapy: A meta-analysis.
Notice bibliographique
Résumé
579 Background: The Katherine trial reported a 3-year invasive disease-free survival (DFS) of 77% in patients not achieving pathological complete response (pCR) and continuing on adjuvant trastuzumab. Case series suggest better outcomes and data support that some patients with residual disease have similar outcomes to those with pCR (Steenbruggen et al). The absolute benefit of adjuvant trastuzumab emtansine (T-DM1) would be smaller in patients with favourable outcomes despite residual disease. As such, a more precise estimate of 3-year DFS is needed for treatment planning. Methods: We reviewed reports of randomized trials of neoadjuvant chemotherapy and HER2-directed therapy and extracted the 3-year DFS, a validated surrogate endpoint in HER2-positive early-stage breast cancer. Data were extracted for patients with residual disease and with pCR. The mean 3-year DFS weighted by study sample size was calculated. Meta-regression comprising linear regression weighted by sample size (mixed effects) was performed to explore associations between 3-year DFS and trial-level patient, disease and treatment factors and changes in 3-year DFS over time. Quantitative significance was explored using methods described by Burnand et al. Results: Eleven studies comprising 3908 patients were included in the analysis. The mean 3-year DFS for patients with pCR and for residual disease was 90.1% and 80.0%, respectively. DFS improved over time. For trials whose final year of accrual was after 2010, mean 3-year DFS for residual disease was 84.7% compared to 78.0% for trials completing accrual before that time (p<0.001). In a subgroup analysis of patients with residual disease, those receiving dual HER2-targeted therapy in the neoadjuvant setting had a 3-year DFS of 85.3% compared to 73.3% for those receiving only trastuzumab (p<0.001). Meta-regression results for residual disease are shown in the Table. Positive quantitative significance was observed for final year of accrual, ER-expression, dual anti-HER2 therapy and concurrent vs sequential anti-HER2 therapy. Negative quantitative significance was observed for larger clinical tumor size and nodal involvement. Conclusions: 3-year DFS for patients with residual disease and HER2-targeted therapy is better than reported in the Katherine trial and has improved over time, possibly due to increased use of dual HER2-targeted therapy in the neoadjuvant setting. In this context, the absolute benefit of adjuvant T-DM1 may be smaller than anticipated. [Table: see text]
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 | 0,052 | 0,060 |
| Méta-épidémiologie (sens strict) | 0,003 | 0,002 |
| Méta-épidémiologie (sens large) | 0,018 | 0,078 |
| Bibliométrie | 0,006 | 0,005 |
| Études des sciences et des technologies | 0,001 | 0,001 |
| Communication savante | 0,004 | 0,002 |
| Science ouverte | 0,003 | 0,002 |
| Intégrité de la recherche | 0,003 | 0,004 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 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 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 ».