Abstract 4682: Sunitinib (SU) in advanced NSCLC: Correlation of circulating biomarkers with clinical outcome
Notice bibliographique
Résumé
Abstract Introduction SU is an oral multitargeted inhibitor of VEGFRs, PDGFRs, KIT, FLT3, CSF-1R and RET. Antitumor activity and safety of SU in NSCLC were reported in phase II trials. We investigated potential biomarkers of clinical outcome with SU in NSCLC. Methods Patients (pts) with Stage IIIB/IV NSCLC in two phase II trials received single-agent SU either as maintenance therapy (n=66: 50 mg/day on Schedule 4/2 [6-week cycle: 4 weeks on followed by 2 weeks off treatment]) following first-line paclitaxel/carboplatin, or as refractory treatment (n=63: 50 mg/day on Schedule 4/2 for up to 9 cycles, or n=47: 37.5 mg/day on a continuous daily dose [CDD] schedule of 4-week cycles for up to 13 cycles). Soluble (s) plasma proteins (VEGF-A, VEGF-C, sVEGFR-2, sVEGFR-3, sE-selectin, sKIT) assayed by ELISA pre-dose and at regular intervals in both trials were analyzed for association with efficacy. Results In the trial of SU maintenance therapy, median progression-free survival (PFS) and overall survival (OS) were greater for pts with sVEGFR-3 levels < median ratio to baseline (BL) (n=10) vs. pts with sVEGFR-3 levels ≥ median ratio to BL (n=11) at Cycle 3 Day 1 (PFS: hazard ratio [HR] 3.6, 95% CI 1.19-11.13, p=0.0153; OS: HR 3.8 [1.35-10.88] p=0.0074). Median PFS was also greater for pts with VEGF-C levels ≥ median ratio to BL (n=15) vs. pts with VEGF-C levels < median ratio to BL (n=15) at Cycle 2 Day 28 (HR 0.3 [0.12-0.80] p=0.0109), a similar but non-significant trend was observed for OS. While PFS did not differ based on sE-selectin levels, pts with sE-selectin levels < median ratio to BL had greater median OS vs. pts with sE-selectin levels ≥ median ratio to BL at Cycle 3 Day 1 (n=8 vs. n=8: HR 4.4 [1.09-17.56] p=0.0241) and end of treatment (n=8 vs. n=9: HR 3.4 [1.10-10.41], p=0.0251). sVEGFR-3 median ratios to BL for pts with complete response (CR), partial response (PR) or stable disease (SD) ≥6 weeks (n=15) were lower vs. progressive disease (PD, n=5) at Cycle 3 Day 1 (0.57 vs. 0.92 p=0.029). In the trial of SU in refractory NSCLC, for Schedule 4/2 VEGF-A mean ratios to BL were higher in pts with CR/PR/SD ≥6 weeks (n=24) vs. PD (n=23) at Cycle 1 Day 14 (4.1 vs. 2.5 p=0.046). sVEGFR-2 and sVEGFR-3 mean ratios to BL were lower in pts with CR/PR/SD ≥6 weeks vs. PD at Cycle 2 Day 28 (0.4 [n=22] vs. 0.6 [n=8] p=0.03) and Cycle 1 Day 28 (0.3 [n=23] vs. 0.4 [n=19] p=0.043), respectively. In the CDD cohort, sVEGFR-2 mean ratios to BL were greater in pts with PFS ≥ median vs. PFS < median at Cycle 3 Day1 (0.5 [n=13] vs. 0.4 [n=4] p=0.032). Mean BL sVEGFR-3 levels were lower in pts with PR/SD vs. PD (41,498 [n=10] vs. 56,210 [n=20] pg/mL p=0.02). No significant difference in sKIT BL levels or ratios to BL were observed and no further strong correlations were apparent for other analytes in either cohort. Conclusions Soluble protein levels at some timepoints correlate with clinical outcome in advanced NSCLC pts treated with SU; low sVEGFR-3 levels were associated with favorable outcome in all analyses. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4682.
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 | 0,000 |
| 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 ».