601 Identification of non-squamous NSCLC molecular subtypes and association with outcomes in the phase 3 IMpower150 study of 1L atezolizumab ± bevacizumab + carboplatin-paclitaxel in metastatic NSCLC
Notice bibliographique
Résumé
<h3>Background</h3> The phase 3 IMpower150 trial showed significantly improved progression-free survival (PFS) and overall survival (OS) with atezolizumab plus bevacizumab plus carboplatin-paclitaxel (ABCP) versus bevacizumab plus carboplatin-paclitaxel (BCP) in chemotherapy-naive patients with non-squamous metastatic NSCLC, regardless of tumor PD-L1 status. Based on these findings, ABCP became an approved first-line treatment for metastatic non-squamous NSCLC. No clinical benefit was seen with atezolizumab plus carboplatin-paclitaxel (ACP) versus BCP in the intent-to-treat population. Our objectives were to characterize the molecular subtypes of non-squamous NSCLC and to explore the relationship between molecular subtype, PD-L1 status and clinical outcomes with ABCP, ACP and BCP. <h3>Methods</h3> RNA sequencing of 564 primary pre-treatment non-squamous NSCLC tumor samples from IMpower150 was analyzed in the ACBP (n=195), ACP (n=178) and BCP (n=185) treatment arms; 6 samples were from patients who were not treated. Non-negative matrix factorization (NMF) was applied to variably expressed genes to define non-squamous molecular subtypes. Tumor PD-L1 levels for each subtype were determined by SP263 immunohistochemistry (Ventana). OS and PFS in each treatment arm were analyzed by NMF subtype. <h3>Results</h3> Four molecular subtypes were identified. NMF1 (n=103) had high enrichment of endothelial cells, neutrophils and basal/squamous-like cells. NMF2 (n=184) had enrichment of mature dendritic cells, macrophages, monocytes and proliferation. NMF3 (n=158) had the highest enrichment of adenocarcinoma and the lowest levels of squamous and CD8+ T-cells, monocytes and alveolar macrophages. NMF4 (n=119) had the most lymphocyte-inflamed transcriptomic profile, with high enrichment of epithelial-to-mesenchymal transition and B, dendritic, stromal and T cells. PD-L1 expression was significantly higher in NMF2 and NMF4 than in NMF1 and NMF3 (<i>P</i>=7.34e-10). Patients with NMF1 and NMF4 had significantly longer PFS with ABCP than ACP or BCP (<i>P</i>=0.009 and <i>P</i><0.0001, respectively; table 1). Those with NMF2 and NMF3 showed no differences in PFS between treatments. Patients with NMF1 showed significantly longer OS with ABCP than other treatments (HR for ABCP vs BCP: 0.51 [95% CI, 0.29–0.90]; <i>P</i>=0.019). In patients with NMF4, median OS was 35.4, 17.6 and 21.7 months with ABCP, ACP and CPB, respectively (HR for ABCP vs BCP: 0.59 [95% CI: 0.34, 1.03]; <i>P</i>=0.059). <h3>Conclusions</h3> Four molecular subtypes of treatment-naive, non-squamous, metastatic NSCLC with different immune-cell and tumor microenvironmental features were characterized. Two subtypes had high tumor PD-L1 expression but different immune-cell profiles and clinical outcomes with ABCP. NMF4 may identify a subset of patients with advanced non-squamous NSCLC who benefit uniquely from 1L ACBP treatment. Further investigation is required. <h3>Acknowledgements</h3> Medical writing support was provided by Samantha Santangelo, of Health Interactions, Inc. This study was funded by F. Hoffmann-La Roche, Ltd. <h3>Trial Registration</h3> NCT02366143 <h3>Ethics Approval</h3> The study was conducted in accordance with the International Conference on Harmonisation Good Clinical Practice guidelines and with the principles of the Declaration of Helsinki. All patients provided written informed consent. An independent data monitoring committee reviewed safety data. The protocol was approved by independent ethics committees at each participating site.
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 | 0,001 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 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 ».