Abstract CT302: Pharmacokinetics (PK) and safety of ARN-509 with abiraterone acetate (AA) and prednisone (P) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC)
Notice bibliographique
Résumé
Abstract Background: ARN-509 and AA target the androgen axis via different mechanisms and may have complementary activity in mCRPC. ARN-509, a potent and selective androgen receptor (AR) antagonist, inhibits AR nuclear translocation and DNA binding without significant AR agonist properties (Clegg et al. Cancer Res. 2012). AA is the prodrug of abiraterone, which directly inhibits androgen biosynthesis. No overlapping toxicities are expected for the combination. This ongoing phase Ib study evaluates the potential PK drug-drug interaction and safety of ARN-509 in combination with AA + P. Methods: Pts had progressive mCRPC and ECOG score ≤ 2. Pts received AA (1000 mg/d) + P (5 mg BID) beginning on Cycle 1 Day 1 (C1D1) with the addition of ARN-509 (240 mg/d) on C1D8 in 28-day treatment cycles until disease progression or toxicity. Serial blood samples for PK analysis were collected on C1D7 and C2D8 for abiraterone analysis and on C2D8 for ARN-509 analysis. Primary objective: evaluate effect of ARN-509 on abiraterone PK. Secondary objective: evaluate safety of ARN-509 in combination with AA + P. Results: As of November 21, 2014, 28 pts have been enrolled. At baseline, the median age was 70 years (range: 49-83); median prostate-specific antigen was 56.8 μg/L (range: 4.1-2597.0 μg/L); bone, nodal, and visceral disease were present in 24 (86%), 17 (61%), and 8 (29%) pts; and 13 (46%) pts were pretreated with docetaxel, 11 (39%) with AA, and 12 (43%) with enzalutamide. 9 pts thus far completed 1 cycle, 6 completed 2 cycles, and 4 completed 3 cycles. 26 pts are continuing therapy. 10 pts were evaluable for PK assessment and 28 pts were evaluable for safety assessment. Most drug-related adverse events (AEs) were grade 1-2, and included fatigue (n = 5), diarrhea (n = 3), dysgeusia (n = 3), vomiting (n = 4), abdominal pain (n = 2), anorexia (n = 3), dyspepsia (n = 2), rash (n = 2) and nausea (n = 3). Grade 3 drug-related AEs included hyponatremia (n = 1), fatigue (n = 1), and increased alanine aminotransferase (n = 1), and were managed by drug interruption and supportive measures. Interim data indicate a small reduction in abiraterone PK exposure when AA + P is coadministered with ARN-509. PK of ARN-509 were consistent with historical data when ARN-509 was given as monotherapy. Conclusions: This ongoing phase Ib study (NCT02123758) indicates no clinically significant PK interaction between ARN-509 and AA + P. The combination is well tolerated in pts with mCRPC; interim AE data were consistent with those seen in the AA + P phase III trials (Fizazi et al. Lancet Oncol. 2012; Ryan et al. NEJM. 2013). These preliminary results justify further evaluation of the safety and efficacy of ARN-509 in combination with AA + P for mCRPC. Citation Format: Edwin M. Posadas, Kim N. Chi, Ronald de Wit, Maja JA de Jonge, Gerhardt Attard, Terence Friedlander, Margaret Yu, Peter Hellemans, Caly Chien, Charlene Abrams, Martha Gonzalez, Géralyn C. Trudel, Vijay Chauhan, Fred Saad. Pharmacokinetics (PK) and safety of ARN-509 with abiraterone acetate (AA) and prednisone (P) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC). [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr CT302. doi:10.1158/1538-7445.AM2015-CT302
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 | 0,000 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 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) | 0,003 | 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 ».