59 DetermaIO (IO score) is associated with efficacy of ICI monotherapy in advanced NSCLC patients: a retrospective BC Cancer study
Notice bibliographique
Résumé
<h3>Background</h3> Immune checkpoint inhibitors (ICI), either as monotherapy or in combination with platinum-based chemotherapy, is standard of care in aNSCLC. However, most patients do not respond to ICI therapy, even when PD-L1≥50% (PD-L1 high). At BC Cancer, only those patients with PD-L1 high are eligible for first line (1L) ICI monotherapy, offering an opportunity to study potential new biomarkers in a relatively unbiased cohort of patients treated by ICI without chemotherapy. DetermaIO (IO score) is a 27-gene RT-qPCR immuno-oncology assay that classifies the tumor immune microenvironment (TIME) as IO+ or IO- and has been previously shown to associate with clinical benefit to ICI therapy in multiple tumor types. <h3>Methods</h3> All available FFPE blocks were assembled for ECOG≤2 patients treated with at least one cycle of ICI monotherapy in the 1L (required to be PD-L1≥50%) or later line (2L+). DetermaIO was performed using a CAP/CLIA validated RT-qPCR assay for cases where sufficient tissue was available. IO score classification was analyzed for association with PFS and OS in patients treated in the 1L. <h3>Results</h3> Considering the entire cohort of 147 patients, DetermaIO was significantly associated with OS (HR=0.68, 95%CI 0.47–0.89, p=0.042) and PFS (HR=0.62, 95%CI 0.43–0.88, p=0.0069). When examining the cohort by line of therapy, 78 (53%) were treated in 1L with ICI monotherapy and were all PD-L1 high. DetermaIO in this subgroup was significantly associated with PFS (HR=0.55, 95%CI 0.32–0.94, p=0.028) and demonstrated meaningful clinical benefit when measuring OS (HR=0.60, 95%CI 0.34–1.06, p=0.078). The objective response rate in the 1L subgroup was 53% for IO+ (2CR, 28PR out of 56 patients) and 23% for IO- (5PR out of 22 patients). The net reclassification rate of IO- amongst the PD-L1 high 1L group was 54.5% (12/22, p<0.01) for response. <h3>Conclusions</h3> Retrospective analysis of outcomes of aNSCLC patients treated 1L with ICI monotherapy found that DetermaIO was significantly associated with PFS and trended towards significance for OS. First-line PD-L1 high patients who were IO- had significantly worse outcomes for PFS than PD-L1 high IO+ patients potentially informing the selection of combination therapy in PD-L1 high patients. These data confirm and expand previous studies of DetermaIO in advanced NSCLC and suggest IO score classification may offer significant incremental information for helping to make complex treatment decisions in aNSCLC. <h3>Ethics Approval</h3> This study was approved by the Research Ethics Board (REB) of University of British Columbia (H20–02635). Individual consent for this retrospective analysis and the use of tumor samples for the IO score assay was required for live patients. Consent was waived by the REB for deceased patients.
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 | 0,001 |
| 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 | 0,000 |
| 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 ».