Impact of nirogacestat on pain, a key symptom in patients with desmoid tumors (DT): Results from the phase 3 DeFi study.
Notice bibliographique
Résumé
11564 Background: Pain reduction is a key treatment goal in DT (aggressive fibromatosis): 60% of patients (pts) experience chronic pain. In the phase 3 DeFi trial, nirogacestat (NIRO; n = 70) significantly improved progression-free survival compared with placebo (PBO; n = 72) in pts with progressing DT (HR: 0.29 [95% CI, 0.15–0.55]; P< 0.001). Also as previously reported, NIRO significantly reduced pain severity by 1.50 points (on a 10-point scale) compared with PBO at cycle 10 (28-day cycles; P< 0.001) per the prespecified secondary endpoint of “worst pain” from the Brief Pain Inventory Short Form (BPI-SF). Additional aspects of pain were collected in DeFi to further characterize treatment impact and consistency across multiple pain assessment tools. Methods: In DeFi, pts completed 3 prespecified pain assessment tools through end of treatment: BPI-SF (worst pain), GOunder/Desmoid Tumor Research Foundation DEsmoid Symptom Scale (GODDESS-DTSS pain scale: worst pain, dull pain, shooting pain), European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire (QLQ-C30 pain scale: pain, pain interference with daily activities). Change from baseline (BL) in pain scores was compared between arms; analyses included mixed models for repeated measures to compare change from BL and stratified Cochran-Mantel-Haenszel to compare proportions of pts with clinically meaningful pain reduction (defined using prespecified thresholds) at cycle 10. Cycle 10 was preselected to allow adequate time for a treatment effect to be observed. Results: Statistically significant and clinically meaningful pain reductions were observed with NIRO compared with PBO at cycle 10 across all assessment tools; statistically significant differences between arms occurred as early as cycle 2 and were sustained throughout treatment. At cycle 10, NIRO reduced mean BL pain per GODDESS-DTSS (0–10 range) by 1.78 points (SE = 0.26) and PBO increased pain by 0.32 points (SE = 0.27; P< 0.001). At cycle 10, NIRO reduced mean BL pain per QLQ-C30 (0–100 range) by 22.05 points (SE = 3.38) and PBO increased pain by 7.19 points (SE = 3.64; P< 0.001). Clinically meaningful pain reduction (by ≥2.0 points) per BPI-SF worst pain (0–10 range) was achieved by 72% of pts with NIRO vs 29% of pts with PBO at cycle 10 ( P< 0.001). Per GODDESS-DTSS, clinically meaningful pain reduction (by ≥1.9 points) was achieved by 62% of pts with NIRO vs 19% of pts with PBO at cycle 10 ( P= 0.002). Conclusions: Rapid, sustained, and consistent reductions in different aspects of pain were observed with NIRO compared with PBO across multiple assessment tools in pts with DT. Furthermore, a significantly greater proportion of pts achieved clinically meaningful reductions in pain with NIRO than with PBO. As pain is the most commonly reported symptom, pain reduction should be a key clinical trial endpoint and a key treatment goal in DT. Clinical trial information: NCT03785964 .
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 distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,007 | 0,028 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,002 | 0,000 |
| Bibliométrie | 0,000 | 0,001 |
| 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 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 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 tête enseignante, 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 ».