Post hoc analysis of rashes reported in patients (pts) with <i>BRAF</i> -altered relapsed/refractory (r/r) pediatric low-grade glioma (pLGG) treated with the type II RAF inhibitor tovorafenib in FIREFLY-1.
Notice bibliographique
Résumé
10037 Background: Targeted therapies have become a mainstay in the treatment of pLGG. While effective, toxicities, including cutaneous adverse events (AEs), are common. Tovorafenib received accelerated FDA approval in April 2024 for the treatment of BRAF -altered r/r pLGG in pts ≥6 months of age based on FIREFLY-1 (NCT04775485) trial results. Maculopapular rash, dermatitis acneiform, and erythematous rash were the most commonly reported rashes (Kilburn LB, et al. Nat. Med. 2024). An update on the incidence, recurrence, and resolution of rash AEs in pts who received tovorafenib in FIREFLY-1 is provided. Methods: This post hoc analysis included 137 pts with pLGG (arm 1/registrational: 77; arm 2/extension: 60) treated with ≥1 dose of tovorafenib. Treatment-emergent rashes, graded by investigators, were grouped as maculopapular/erythematous/eczematous (M/E/E) or acneiform/pustular (A/P) (May 10, 2024 data cutoff). A rash episode included all rash events occurring over continuous days. A new rash was any subsequent episode occurring a day or more after the prior episode end date. Results: Median duration of tovorafenib treatment was 21.0 months (mos). 93% (128/137) of pts had a treatment-emergent rash. Of those, 59% (76) had only M/E/E rashes, 11% (14), only A/P rashes, and 30% (38), both types. As expected, A/P rashes occurred more often in pts ≥12 years of age (y/a). The rash was graded as G1 in 36% (46), G2 in 50% (64), and G3 in 14% (18) of pts. Most experienced 1 (53% [68]) or 2 (31% [40]) rash episodes. First rash episode median time to onset (TTO) was 0.43 mos, with 47% (60) G1, 41% (52) G2, and 13% (16) G3. First rash episodes resolved for 74% (95/128) of pts within a median of 2.67 mos. Resolution of first rash was more common among pts with M/E/E vs A/P rashes. Among any rash episodes (27% [58/219]) that remained unresolved, final severity was G1 (22% [48/219]) or G2 (5% [10/219]). All G3 rashes resolved. 47% (60) of pts experienced ≥2 rash episodes, of which 82% (49) were the same/lower grade episode. Of the 11 pts with a more severe second episode, 8 (73%) resolved completely. 80% (102) of pts received standard of care (SOC) treatments for rash, primarily topical steroids/antibiotics, oral antihistamines, and emollients. Only 1 (1%) pt had a rash-related tovorafenib discontinuation. 18% (23) of pts had dose interruptions due to rash. 11% (14) of pts had a dose reduction due to rash; of those, 57% (8) required no additional dose reductions due to rash. Conclusions: Rashes were common in pts treated with tovorafenib in FIREFLY-1. They typically occurred early in treatment, most were G1 or G2, resolved within a median of ~3 mos, and were manageable with SOC treatment and/or tovorafenib dose modifications. A/P rashes occurred more frequently in pts ≥12 y/a; there were no other significant trends in rashes experienced between the two age groups. Clinical trial information: NCT04775485 .
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 | 0,004 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,003 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,006 | 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 ».