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 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 | 0,003 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,002 | 0,001 |
| Méta-épidémiologie (sens large) | 0,003 | 0,001 |
| Bibliométrie | 0,001 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,001 | 0,001 |
| Intégrité de la recherche | 0,001 | 0,003 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,009 | 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 ».