Nilotinib Responses and Tolerability Confirmed in North American Patients with Chronic Myeloid Leukemia (CML) From ENACT (Expanding Nilotinib Access in Clinical Trials).
Notice bibliographique
Résumé
Abstract 3295 Poster Board III-1 Background: Nilotinib is a potent and highly selective BCR-ABL kinase inhibitor, approved for the treatment of patients (pts) with Philadelphia chromosome-positive chronic myelogeneous leukemia (Ph+ CML) in chronic phase (CP) and accelerated phase (AP) who are resistant or intolerant to prior therapy, including imatinib. The open label, multicenter ENACT study was initiated as a global expanded access program to obtain additional safety information in CML pts in a clinical practice setting outside of a registration study. This report focuses on a subset of patients enrolled in North America. Methods: Adult patients with imatinib resistant or -;intolerant Ph+ CML-CP, AP or BC were admitted to the study. The definition of imatinib resistance and intolerance were the same as the pivotal phase II registration study and pts could have been previously treated with other TKIs in addition to imatinib. Patients with impaired cardiac function, concurrent severe medical conditions or taking prohibited medications were excluded. Pts received nilotinib 400 mg twice daily (BID). Dose escalation was not permitted. Pts who required dose reduction to 400 mg once daily due to toxicity were allowed to have a dose re-escalation to 400 mg BID after resolution of the adverse events (AEs), lack of response, or persistent disease at the investigator's discretion. Results: A total of 207 North American pts were enrolled in the ENACT study between 01/2006 and 10/2008, including 172 CP pts (83%), 15 AP pts (7%) and 20 BC pts (10%). The median age of all pts was 54 years; 53% were imatinib-resistant, 45% were imatinib-intolerant, and 1.4% were resistant/intolerant. The most common prior anti-neoplastic therapy (other than imatinib) was hydroxyurea (73% of CP pts, 87% of AP pts, and 90% of BC pts), followed by dasatinib (32% of CP pts, 40% of AP pts, and 30% of BC). At study completion, 100 pts (48%) were continuing on nilotinib and 107 pts (52 %) discontinued treatment; 29 (17%) CP pts, 7 (47%) AP pts, and 14 (70%) BC pts discontinued due to disease progression. There were a total of 7 (3.4%) deaths during the study. Patient disposition is summarized in Table 1. Median (range) duration of nilotinib exposure was 227 (1-807) days for CP pts, 78 (15-426) days for AP pts, and 73 (8-571) days for BC pts; median average dose intensity was 766, 785 and 766 mg/day, respectively. Thirty-five CP pts (20%), 3 AP pts (20%) and 6 BC pts (30%) had their dose reduced due to AE, while 75 CP pts (44%), 5 AP pts (33%), and 8 BC pts (40%) had their dose interrupted due to AE. Median duration of dose interruption due to AE was short (8 days for CP and BC pts and 3 days for AP pts). The most common grade 3/4 hematologic AEs suspected of being drug related were thrombocytopenia (12% of CP pts, 20% of AP pts, and 15% of BC pts) followed by neutropenia (9% of CP pts, 27% of AP pts, and 15% of BC pts). The most frequent non hematologic all grades AEs or lab abnormalities included rash, headache, nausea, fatigue and hyperbilirubinaemia, and all were slightly higher in North American patients compared with the overall ENACT population. No patients discontinued treatment due to pleural effusion and there was no incidence of QTcF prolongation > 500 msec. Overall, major cytogenetic responses (MCyR) rates were 49% in CP, 27% in AP and 20% in BC pts, while complete cytogenetic responses (CCyR) rates were 36% in CP, 7% in AP and 20% in BC pts. Conclusions: ENACT is the largest dataset from a single CML study of the available TKIs that further demonstrates that nilotinib is generally well tolerated in pretreated patients in all phases of CML. The safety profile in this study is similar to that observed the pivotal phase II registration study, as are the cytogenetic response rates, with a maintenance of high dose intensity. This data supports the use of nilotinib at 400 mg BID as the recommended dose in these CML populations. Disclosures: Powell: Novartis Pharmaceuticals: Research Funding. Khoury:BMS: Honoraria; Wyeth: Honoraria; Novartis Pharmaceuticals: Honoraria; Chemgenex: Honoraria; Genzyme: Honoraria. Rizzieri:Novartis Pharmaceuticals: Honoraria, Research Funding, Speakers Bureau. Williams:Novartis Pharmaceuticals: Employment. Turner:Novartis Pharmaceuticals: Research Funding, Speakers Bureau; BMS: Research Funding, Speakers Bureau; wyeth: Research Funding.
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 | 0,002 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| 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 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 ».