Abstract CT537: A phase 2, multicenter, randomized, double-blind trial of maintenance therapy with FLT3 inhibitor gilteritinib (ASP2215) in patients with FLT3/ITD AML (GOSSAMER study)
Notice bibliographique
Résumé
Abstract Background: Patients with acute myeloid leukemia (AML) in remission are at high risk of relapse, warranting remission-prolonging therapy. Gilteritinib is the first FMS-like tyrosine kinase 3 (FLT3) inhibitor approved as monotherapy in FLT3-mutated relapsed/refractory AML. The aim of the study was to compare relapse-free survival (RFS) in patients with FLT3/internal tandem duplication AML in first complete remission who received gilteritinib or placebo. Method: In this phase 2, double-blind trial, patients were randomized 2:1 to gilteritinib (120 mg) or placebo once daily for up to 2 years, beginning after completion of induction/consolidation (I/C) therapy. RFS, defined as time from randomization date until the date of documented relapse or death from any cause was assessed via independent review committee adjudication (primary efficacy endpoint). Overall survival (OS) was defined as the time from date of randomization until date of death from any cause. Survival and treatment-emergent adverse events (TEAEs) were assessed 30 days after treatment discontinuation, and every 3 months thereafter. Due to a slow accrual rate, this trial (NCT02927262) was changed from a planned phase 3 to phase 2 based on the reduction in sample size. Results: 124 patients were screened and 98 were randomized (gilteritinib 63, placebo 35) and are included in the full analysis set (FAS), of whom 32 (gilteritinib 20, placebo 12) completed 2 years of treatment. The safety analysis set (SAF) comprised 97 patients (gilteritinib 62, placebo 35) who had received ≥1 dose of study drug. In the FAS, relapse occurred in 31/63 (49.2%) gilteritinib- and 20/35 (57.1%) placebo-treated patients; 3/63 (4.8%) gilteritinib-treated patients died without relapse. RFS was not significantly improved with gilteritinib vs placebo (hazard ratio [HR] 0.738, 95% confidence interval [CI] 0.407-1.336; 1-sided stratified log-rank p-value 0.163). Median RFS was 24.02 months for gilteritinib and 15.84 months for placebo. OS in the FAS was not significantly different between treatments (gilteritinib 21/63, [33.3%], placebo 11/35 [31.4%]; HR 1.130, 95% CI 0.540-2.364; 1-sided stratified log-rank p-value 0.627). Median OS was not reached in either arm. TEAEs in the SAF occurred in 58/62 (93.5%) gilteritinib- and 33/35 (94.3%) placebo-treated patients including, respectively, 51/62 (82.3%) and 20/35 (57.1%) drug-related TEAEs and 10/62 (16.1%) and 3/35 (8.6%) serious drug-related TEAEs. The most common TEAEs were increased blood creatine phosphokinase (gilteritinib 18/62 [29.0%], placebo 1/35 [2.9%]) and thrombocytopenia (gilteritinib 12/62 [19.4%], placebo 4/35 [11.4%]). Conclusion: Gilteritinib showed improved RFS versus placebo, but the difference was not statistically significant. There were no new safety findings in the gilteritinib arm. Citation Format: Mark D. Minden, Jacob M. Rowe, Emmanuel Gyan, Kohmei Kubo, Nahla Hasabou, David Delgado, Wensheng He, Stanley C. Gill, Jason E. Hill, Ramon Tiu. A phase 2, multicenter, randomized, double-blind trial of maintenance therapy with FLT3 inhibitor gilteritinib (ASP2215) in patients with FLT3/ITD AML (GOSSAMER study) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT537.
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) | 0,002 | 0,001 |
| Méta-épidémiologie (sens large) | 0,002 | 0,001 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,002 | 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 ».