Abstract A105: Phase 2 trials of linifanib (ABT-869) in advanced hepatocellular, renal cell and non-small cell lung cancer: Associations of response by CT or DCE-MRI with patient outcome
Notice bibliographique
Résumé
Abstract Background: Linifanib is a novel orally active and selective inhibitor of VEGF and PDGF families of receptor tyrosine kinases. Linifanib has demonstrated antitumor activity in a variety of advanced solid tumors in phase 1 and 2 trials. The objective of this analysis was to assess associations between pt outcome (PFS or OS) and response by CT (per RECIST or tumor volume change), or DCE-MRI (per Ktrans), in patients (pts) enrolled in ongoing phase 2 linifanib monotherapy trials. Methods: Three open-label, phase 2 monotherapy studies were conducted internationally in advanced/metastatic solid tumor pts with hepatocellular carcinoma (HCC), non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC). Interim efficacy and safety results have been previously reported. A retrospective exploratory analysis of associations between pt outcome and CT or DCE-MRI response was conducted. An independent centralized review of tumor response assessment by CT (baseline, and Q8 wks) and DCE-MRI (baseline, and 2 wks) was performed using a uniform charter. CT assessed tumor volume and best percent change from baseline and pts were classified as PR, SD, or PD by RECIST. Baseline Ktrans and percent change in Ktrans were derived from DCE-MRI. Statistical analysis was performed using the Cox proportional hazard model and logrank test, and significance considered at the level of P≥0.05. Threshold estimates were determined by the Bootstrapping & Aggregating Thresholds from Trees (BATTing). Results: Across the 3 phase 2 trials, 236 pts were enrolled from 08/07 to 10/08 at 34 centers: 44 pts with HCC, 53 pts with RCC, and 139 pts with NSCLC. Based on the BATTing methodology, 79/191 evaluable pts had a maximum CT tumor volume decrease of >32%. This was associated with improved OS (log-rank p<0.001) and PFS (log-rank p<0.001). Pts with confirmed or unconfirmed PR (n=27) per RECIST had better OS (p=0.021) and PFS (p=0.017) than those who did not achieve a PR (n=181). Among the 236 pts, 117 had DCE-MRI scans at baseline and Day 15. Of these, 68/117 pts (58%) had baseline Ktrans above the BATTing cutoff of 0.055 and this was associated with improved OS (log-rank, p=0.011), but not PFS (log-rank, p=0.835). DCE-MRI response (Ktrans decrease) at 2 wks was not associated with significant improvement in PFS or OS. Conclusions: CT tumor volume reduction and CT response were associated with improved OS and PFS. Greater baseline Ktrans was associated with improved OS but not PFS. Ktrans changes at 2 wks were not associated with improvement in pt outcome. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):A105.
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 | 0,000 | 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) | 0,000 | 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 ».