Recurrent or metastatic salivary gland tumor (MSGT) patients treated with selinexor, a first in class selective exportin-1 (XPO1) inhibitor.
Notice bibliographique
Résumé
6586 Background: MSGT are rare with limited systemic treatments. This single institution, prospective study in recurrent or metastatic (RM) MSGT involved 2 phases: genomic profiling followed by treatment with either genomically-matched or unmatched therapy. Here we present the results of the unmatched arm for patients (pts) treated with S an oral selective inhibitor of XPO1 that leads to activation of tumor suppressor proteins and retention of oncoprotein mRNAs in the cell nucleus, inducing cancer cell apoptosis. Methods: Patients (pts) with RM-MSGT had archived paraffin embedded tumor samples profiled with targeted next generation sequencing, immunohistochemistry for androgen receptor (AR) and fluorescent in-situ hybridization for HER-2 and ALK. If no actionable mutations were identified or if no matched agents were available, pts with progressive disease could receive S (60mg given twice weekly Q28 days). The study had a simon-2 stage design; 1 partial response in the first 18 pts treated with S, would trigger an additional 7pts to receive S in stage 2. Results: Between July 2014 and April 2019 85 pts were enrolled on study: 73 had sequencing which identified 41 with no actionable mutations and 32 with actionable mutations. 18 pts (10F/8M, median age 61 years [40-79]) were treated with S and included adenoid cystic (n = 8), salivary duct (n = 4), acinic cell (n = 2) and other subtypes (n = 4). Of these 18, 4 pts had actionable aberrations: AR amplification (n = 2), mutations in SMARCB1 (n = 1) and CDKN2A (n = 1). 13pts were treatment naïve, 3pts and 2pts received 1 and 2 or more lines of treatment respectively prior to enrollment: androgen deprivation therapy (n = 2), chemotherapy (n = 3), early phase clinical trials (n = 3). The median number of cycles of S received were 3 (range: 1-19). The best response by RECIST was SD in 13pts (72%) (SD > 6 months (range: 6-18 months) in 5pts (28%); tumor reduction measured in 7pts (39%)), no PRs, PD in 3pts (17%), and 2pts (11%) were not evaluable for response due to insufficient duration of treatment coming off early due to toxicity. The median PFS (95% CI) was 7.6 (3.5-NA) months and the median OS (95% CI) was 15.4 (7.3-NA) months. The most common drug-related toxicities were grade 1-2 fatigue 14pts (78%), nausea 13pts (72%) and dysguesia 10pts (56%). 5 (28%) pts had a dose reduction and 6 (33%) in total had a dose interruption due to toxicity. Conclusions: Single agent antitumor activity was limited and the side effect profile was tolerable. No specific genomic aberration was associated with response to S. Clinical trial information: NCT02069730 .
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 | 0,000 |
| 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 | 0,000 | 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) | 0,001 | 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 ».