Abstract 4660: A randomized phase II study of the telomerase inhibitor imetelstat as maintenance therapy for advanced non-small cell lung cancer.
Notice bibliographique
Résumé
Abstract Tumor regrowth after chemotherapy may be driven by growth of tumor ‘stem cells’. Telomerase, required for indefinite replication, is upregulated in tumor progenitor cells. Imetelstat is a 13-mer oligonucleotide which is a potent and specific telomerase inhibitor. Progression-free survival (PFS) and the duration of responses after 1st-line chemotherapy for non-small-cell lung cancer (NSCLC) are short, which has led to an interest in developing active maintenance therapies. A randomized phase II study was conducted to assess whether imetelstat, given as maintenance therapy, prolongs PFS in NSCLC. Pts were eligible with advanced NSCLC not progressing after completing 4-6 cycles of platinum-based doublet induction chemotherapy, any NSCLC histology, performance status (PS) ECOG 0 or 1, and not scheduled to receive maintenance with pemetrexed or erlotinib. Pts were randomized 2:1 to imetelstat 9.4 mg/kg (d1 and 8 of a 21d cycle) or observation until progressive disease or unacceptable toxicity (concomitant use of bevacizumab was permitted). The 1o endpoint was PFS; safety/tolerability and objective response rate were 2o endpoints. 116 pts were enrolled between Jul 2010 to Apr 2012, with 114 completing a first visit (i.e. efficacy population). Baseline characteristics of age, gender, PS and number of induction cycles were well balanced. 18.4% had squamous histology; 31.6% received concomitant bevacizumab (bev). The median number of imetelstat maintenance cycles was 3. In the overall analysis of PFS, a non significant improvement in favor of the imetelstat arm was observed (HR = 0.77, P=0.295, 95% CI 0.48 - 1.25). Median PFS was 2.8m for imetelstat and 2.6m for control. In the subgroup of patients who did not receive bevacizumab, the HR was 0.59 (vs. 1.07 for the bevacizumab subgroup; interaction P=0.15). The objective response rate was 4.3% in the imetelstat arm and 2.8% in the control arm. Six month overall survival was 80% for imetelstat and 72% for control (HR = 0.86, P=0.642, 95% CI 0.44 - 1.66). Imetelstat was generally well tolerated although hematologic toxicity, predominantly neutropenia and thrombocytopenia, was increased in the imetelstat arm (grade 3/4 neutropenia 18% for imetelstat vs 0% for control, grade 3/4 thrombocytopenia 37% for imetelstat vs 0% for control). The most frequent non-hematologic toxicities were fatigue (imetelstat 42.1% vs control 18.4%), nausea (43.4% vs 7.9%), vomiting (25.0% vs 5.3%) and anaemia (19.7% vs 5.3%). The overall findings suggest that imetelstat has modest, but not clinically meaningful, activity as a maintenance therapy in pts with NSCLC. A pre-specified exploratory subgroup analysis of PFS by tumor telomere length is reported separately. Citation Format: Alberto Chiappori, Tatjana Kolevska, Bart Burington, David Spigel, Steven Hager, Mark Rarick, Shirish Gadgeel, Normand Blais, Joachim Von Pawel, Lowell Hart, Martin Reck, Joan Schiller. A randomized phase II study of the telomerase inhibitor imetelstat as maintenance therapy for advanced non-small cell lung cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4660. doi:10.1158/1538-7445.AM2013-4660
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 | 0,003 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,002 | 0,001 |
| Méta-épidémiologie (sens large) | 0,003 | 0,001 |
| Bibliométrie | 0,001 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,002 | 0,003 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,008 | 0,002 |
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 ».