Larotrectinib (laro) long-term efficacy and safety in patients (pts) with tropomyosin receptor kinase (TRK) fusion thyroid carcinoma (TC).
Notice bibliographique
Résumé
6091 Background: Neurotrophic tyrosine receptor kinase ( NTRK) gene fusions are oncogenic drivers in a variety of tumor types, including TC. Laro is a first-in-class, highly selective, central nervous system (CNS)-active TRK inhibitor approved for tumor-agnostic use in pts with TRK fusion cancer based on a rapid, robust, and durable objective response rate (ORR) in both adult and pediatric pts with various cancers. Here, we report data on the subset of pts with TRK fusion TC treated with larotrectinib with long-term follow-up. Methods: Pts with TRK fusion TC enrolled in three laro clinical trials (NCT02576431, NCT02122913, NCT02637687) were included. Laro was administered at 100 mg twice daily to most pts; two pediatric pts received 100 mg/m2. Responses were assessed per independent review committee (IRC) using RECIST v1.1. Data cut-off: July 20, 2022. Results: As of data cut-off, 30 pts were eligible for efficacy assessment by IRC. The median age was 61.5 years (range 6–80) and the median time since initial cancer diagnosis was 5.0 years (range 0–46). The gene fusions involved NTRK1 (n =14; 47%) or NTRK3 (n =16; 53%). Fifteen pts (50%) received no prior systemic therapies, and six (20%) received ≥2; 23 (77%) received prior radioiodine. ORR was 63% (95% confidence interval [CI] 44–80): three (10%) complete response, 16 (53%) partial response (PR), five (17%) stable disease, four (13%) progressive disease, and two (7%) not evaluable. For pts classified as differentiated TC (DTC; n = 23), the ORR was 78% (95% CI 56–93). For pts classified as anaplastic TC (ATC; n = 7), the ORR was 14% (95% CI 0–58). All four pts with CNS metastases at baseline had a PR. Median time to response was 1.9 months, and median duration of response (DoR) was 43.3 months (95% CI 21.6–not estimable [NE]) at a median follow-up of 32.3 months. Median progression-free survival was 35.5 months (95% CI 23.4–NE) at a median follow-up of 34.0 months. Median overall survival (OS) was not reached (NR; 95% CI 48.7–NE) at a median follow-up of 46.4 months; the 48-month OS rate was 71% (95% CI 54–88). Median OS was NR (95% CI 48.7–NE) in DTC and 8.8 months (95% CI 2.6–NE) in ATC. At data cut-off, five pts who had disease progression continued treatment for ≥4 weeks due to continued clinical benefit. Treatment-related adverse events (TRAEs) were predominantly Grade 1–2. Grade ≥3 TRAEs were reported in two (7%) pts (anemia and decreased lymphocyte count). There were no treatment discontinuations due to TRAEs. Conclusions: Laro continues to demonstrate a rapid and durable response, extended survival, and a favorable safety profile in pts with TRK fusion DTC. Limited single-agent activity was observed in ATC. These results support the wider adoption of next generation sequencing panels, which include NTRK gene fusions, in pts with advanced TC prior to the initiation of any systemic therapy. Clinical trial information: NCT02576431 , NCT02122913 , NCT02637687 .
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 | 0,001 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| 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) | 0,001 | 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 ».