Abstract CT104: Efficacy of pembrolizumab (MK-3475) and relationship with PD-L1 expression in patients with non-small cell lung cancer: Findings from KEYNOTE-001)
Notice bibliographique
Résumé
Abstract Background: Preliminary KEYNOTE-001 data showed that the PD-1 inhibitor pembro has manageable safety and antitumor activity in previously treated and treatment-naive advanced non-small cell lung cancer (NSCLC). In a training set of 182 pts, 129 of whom had measurable disease and tumor evaluable by an IHC clinical trial assay (CTA) for PD-L1 expression, ORR was higher in pts with membranous PD-L1 expression in ≥50% of tumor cells (proportion score [PS] ≥50%) vs PS <50%. We aimed to verify the relationship between PD-L1 expression and ORR in an independent validation set of NSCLC pts enrolled in KEYNOTE-001 and to assess the impact of PD-L1 expression in the combined training and validation sets. Methods: Advanced or metastatic NSCLC pts received pembro 2 mg/kg Q3W, 10 mg/kg Q3W, or 10 mg/kg Q2W. Response was assessed every 9 wk. Treatment decisions were managed per investigator-assessed irRC. Efficacy evaluation was per centrally assessed RECIST v1.1. PD-L1 expression was determined by the CTA. Before analysis, ORR and PD-L1 data from the validation set were merged in pts with measurable disease and CTA-evaluable tumors. Duration of response (DOR), PFS, and OS were assessed in all treated pts from the training and validation sets with CTA-evaluable tumors. Results: In all 495 pts from the training and validation sets, irrespective of PD-L1 expression, ORR was 19.4%, median DOR was 12.4 mo, median PFS was 3.7 mo, and median OS was 12.0 mo. 9% experienced grade 3-5 treatment-related AEs; 4% discontinued due to a treatment-related AE. There was 1 treatment-related death (pneumonitis). Of the 313 pts in the validation set, ORR in the 204 pts evaluable by the CTA was 45.2% in those with PS ≥50% (Table). The relationship between ORR and PD-L1 expression was observed in previously treated and treatment-naive pts (Table). In the 356 pts evaluable by the CTA in the total population, PFS and OS were longer in pts with PS ≥50% (Table). Median OS was not reached in pts with PS ≥50%, regardless of prior treatment. Median (range) DOR was similar in pts with PS ≥50% (12.4 mo [2+ to 22.8+]), 1-49% (10.3 mo [1.4+ to 10.3]), and <1% (NR [0.9+ to 10.8+]). Conclusion: Pembro provides durable antitumor efficacy and safety in pts with treatment-naive and previously treated NSCLC. These data validate that membranous PD-L1 expression in ≥50% of tumor cells identifies pts with advanced NSCLC who are particularly likely to obtain clinical benefit from pembro. Proportion Score (PS)≥50%1-49%<1%ORR in evaluable pts in the validation set,% (95% CI)Totaln = 73n = 103n = 2845.2 (33.5-57.3)16.5 (9.9-25.1)10.7 (2.3-28.2)Previously treatedn = 57n = 77n = 2243.9 (30.7-57.6)15.6 (8.3-25.6)9.1 (1.1-29.2)Treatment naiven = 16n = 26n = 650.0 (24.7-75.3)19.2 (6.6-39.4)16.7 (0.4-64.1)Survival in evaluable pts in the total population, mo, median (95% CI)PFSTotaln = 119n = 161n = 766.3 (2.9-12.5)3.3 (2.1-4.1)2.3 (2.1-4.0)Previously treatedn = 99n = 127n = 686.1 (2.1-12.5)2.3 (2.1-3.4)2.2 (2.0-4.1)Treatment naiven = 20n = 34n = 812.5 (2.4-12.5)4.3 (3.1-6.4)3.5 (2.1-4.2)OS [NR, not reached.]Totaln = 119n = 161n = 76NR (13.7-NR)8.8 (6.8-12.4)8.8 (5.5-12.0)Previously treatedn = 99n = 127n = 68NR (9.3-NR)7.3 (5.8-12.1)8.6 (5.5-12.0)Treatment naiven = 20n = 34n = 8NR (NR-NR)16.2 (8.6-16.2)10.4 (3.4-NR) Citation Format: Edward B. Garon, Naiyer Rizvi, Rina Hui, Natasha B. Leighl, Ani S. Balmanoukian, Joseph P. Eder, Amita Patnaik, Charu Aggarwal, Matthew A. Gubens, Leora Horn, Enric Carcereny, Myung-Ju Ahn, Enriqueta Felip, Jong-Seok Lee, Jin Zhang, Reshma A. Rangwala, Gregory M. Lubiniecki, Charlotte M. Roach, Kenneth Emancipator, Leena Gandhi. Efficacy of pembrolizumab (MK-3475) and relationship with PD-L1 expression in patients with non-small cell lung cancer: Findings from KEYNOTE-001). [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr CT104. doi:10.1158/1538-7445.AM2015-CT104
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 | 0,002 |
| 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 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 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 ».