Abstract 4718: A randomized phase 2 study of the cyclin-dependent kinase (CDK) inhibitor dinaciclib (SCH 727965) in patients with advanced breast cancer
Notice bibliographique
Résumé
Abstract Dinaciclib is a potent, selective inhibitor of CDKs 1, 2, 5, and 9 with preclinical activity in breast cancer cell lines and tumor xenografts. A randomized, multicenter, open-label phase 2 study was conducted to compare the efficacy of dinaciclib and capecitabine (1250 mg PO) in patients (pts) with advanced, previously treated breast cancer (BC). Dinaciclib 50 mg/m2 was administered by 2-hour i.v. infusion once every 21 days. Key inclusion criteria included ≤2 prior chemotherapy regimens, prior treatment with a taxane and anthracycline, and measurable disease. According to the original design, 20 pts were to be randomized 1:1 and thereafter pts were to be randomized using an adaptive Bayesian algorithm that adjusts the randomization ratio in favor of the more active arm. The protocol was amended to continue 1:1 randomization in lieu of the adaptive approach to obtain more experience with upfront dinaciclib. Patients were allowed to cross-over to dinaciclib after progressing on capecitabine. This design provides a comparison of dinaciclib versus capecitabine and an assessment of dinaciclib activity in patients who progressed on capecitabine. Time-to-progression (TTP) was the primary endpoint for pts receiving upfront treatment, and response rate (RR) was the primary endpoint for pts who crossed over to dinaciclib. Twenty-eight pts were treated (13 dinaciclib, 15 capecitabine). Data on 19 dinaciclib treated pts, including 6 that crossed over, are presented. Their median age was 53 (34-80) with a median of 2 (1-2) prior chemotherapy regimens and median ECOG performance status of 1(0-1). ER+/PR+/Her2 receptor status is available for 10/13 pts treated with dinaciclib, including five with ER+/PR+/Her2-, one with ER-/PR-/Her2-, two with ER-/PR-/Her2+ and two with ER+/PR-/Her2-. The median number of treatment cycles was 3 (1-11). 17 pts received more than one cycle of dinaciclib treatement. Investigators reported partial responses (PR) in 2/12 (17%) evaluable subjects receiving upfront dinaciclib; both with ER+/HER2- tumors. One confirmed PR had a complete resolution of a 4 cm chest wall mass. No responses were reported on the cross over arm. Four of fifteen (27%) evaluable subjects receiving capecitabine were reported to have PR. Analysis of TTP will be presented at the meeting. Treatment-related grade 1 and 2 toxicities, occurring in >30% of pts, included diarrhea (67%), nausea (67%), vomiting (61%), neutropenia (50%) and decreased appetite (44%). The most common treatment-related grade 3 and 4 toxicities, occurring in 2 or more pts, were neutropenia (64%), leukopenia (29%), AST increased (14%) and febrile neutropenia (14%). PK results will be included in the final abstract. Dinaciclib monotherapy showed some anti-tumor activity, with acceptable safety and tolerability, in patients with ER+/Her2- BC, warranting further exploration in the combination setting. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4718. doi:10.1158/1538-7445.AM2011-4718
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 | 0,001 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 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 | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 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 ».