Abstract PO-008: Association of plasma Epstein-Barr virus DNA and clinical response in patients with recurrent and/or metastatic nasopharyngeal cancer treated with pembrolizumab or standard-of-care chemotherapy in KEYNOTE-122
Notice bibliographique
Résumé
Abstract Introduction: Plasma Epstein-Barr virus (EBV) DNA has been shown to be a sensitive and specific biomarker for prognosis, surveillance of recurrence, and treatment response of nasopharyngeal cancer (NPC). The phase 3 KEYNOTE-122 trial (NCT02611960) was conducted to evaluate pembrolizumab (pembro) vs standard of care (SOC) chemotherapy (chemo) in patients with platinum-pretreated recurrent/metastatic (R/M) NPC. This exploratory analysis was designed to evaluate association between plasma EBV DNA load and clinical response in patients treated with pembro or SOC in KEYNOTE-122. Materials and Methods: Patients who received ≥1 prior platinum-based chemo with histologically confirmed EBV-positive R/M NPC measurable per RECIST v1.1 and an ECOG PS ≤1, were randomly assigned 1:1 to receive pembro 200 mg IV Q3W for ≤35 cycles or investigator’s choice of SOC chemo (capecitabine, gemcitabine, or docetaxel). Association between baseline plasma EBV DNA load, as measured using a high-sensitivity qPCR assay, and clinical outcomes (ORR, PFS, OS) was evaluated within each treatment arm. Significance of continuous EBV DNA load was prespecified at 0.05 for 1-sided P values from logistic (ORR) and Cox proportional hazard regression (PFS, OS) adjusted for ECOG PS. Additional assessments included association between clinical outcomes and plasma EBV DNA load fold change from baseline at cycle 2, day 1 (C2D1), after baseline adjustment, and descriptive comparison between baseline plasma EBV DNA load and tumor volume in predicting clinical outcomes. Clinical data cutoff: November 30, 2020. Results: 215/228 (94.3%) treated patients had evaluable plasma EBV DNA load data at baseline (pembro, 111; SOC, 104). Baseline plasma EBV DNA load (as a continuous variable) was significantly associated with PFS and OS for pembro and SOC (both P < 0.005) but not ORR (P = 0.105, pembro; 0.473, SOC). Association between plasma EBV DNA load fold change from baseline at C2D1 and ORR, PFS, or OS was P ≤ 0.005 for both pembro and SOC. Baseline plasma EBV DNA load was numerically more predictive of OS and PFS than tumor volume for both pembro (C index [95% CI]: EBV DNA [OS: 0.71, 0.64-0.77; PFS: 0.67, 0.60-0.74] vs tumor volume [OS: 0.47, 0.41-0.54; PFS: 0.42, 0.35-0.49]) and SOC (EBV DNA [OS: 0.67, 0.60-0.73; PFS: 0.64, 0.56-0.71] vs tumor volume [OS: 0.58, 0.51-0.65; PFS: 0.54, 0.46-0.62]). Conclusions: In this post hoc exploratory analysis of KEYNOTE-122, higher baseline plasma EBV DNA load was negatively associated with PFS and OS in patients with NPC treated with pembro or SOC. Independent of baseline association, a larger decrease in plasma EBV DNA load at C2D1 relative to baseline was associated with improved clinical outcomes to both treatments. EBV DNA was more predictive of clinical outcomes than tumor volume. While definitive conclusions are limited, these findings provide additional support for plasma EBV DNA as a prognostic biomarker for NPC, which could guide treatment decisions. Citation Format: Anthony T. C. Chan, Victor Ho Fun Lee, Ruey-Long Hong, Myung-Ju Ahn, Wan Qin Chong, Anna Spreafico, Sung-Bae Kim, Gwo Fuang Ho, Priscilla B. Caguioa, Nuttapong Ngamphaiboon, Ramona F. Swaby, Bo Wei, Andrea Webber, John Kang, Burak Gumuscu, Jianda Yuan, Lillian Siu. Association of plasma Epstein-Barr virus DNA and clinical response in patients with recurrent and/or metastatic nasopharyngeal cancer treated with pembrolizumab or standard-of-care chemotherapy in KEYNOTE-122 [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Innovating through Basic, Clinical, and Translational Research; 2023 Jul 7-8; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2023;29(18_Suppl):Abstract nr PO-008.
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 | 0,001 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,005 | 0,001 |
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 ».