Nivolumab (NIVO) plus chemotherapy (chemo) versus chemo as first-line (1L) treatment for advanced gastric cancer/gastroesophageal junction cancer/esophageal adenocarcinoma (GC/GEJC/EAC): Expanded efficacy, safety, and subgroup analyses from CheckMate 649.
Notice bibliographique
Résumé
240 Background: CheckMate 649 is a randomized, global phase 3 study of 1L programmed death-1 (PD-1) inhibitor–based therapies in advanced non-HER2-positive GC/GEJC/EAC that demonstrated superior overall survival (OS) with NIVO + chemo vs chemo, leading to approvals in the US and other countries. Clinically meaningful long-term survival benefit with NIVO + chemo vs chemo was observed with 24 months (mo) of minimum follow-up in all randomized patients (pts) for both OS (HR 0.79 [95% CI 0.71–0.88]) and progression-free survival (PFS; HR 0.79 [95% CI 0.70–0.89]; Janjigian YY et al; ESMO 2021). We present expanded analyses of NIVO + chemo vs chemo with minimum follow-up of 24 mo. Methods: Adults with previously untreated, unresectable advanced or metastatic GC/GEJC/EAC were enrolled regardless of PD-ligand (L)1 expression. Pts with known HER2-positive status were excluded. Pts were randomized to NIVO (360 mg Q3W or 240 mg Q2W) + chemo (XELOX Q3W or FOLFOX Q2W), NIVO 1 mg/kg + IPI 3 mg/kg Q3W (4 doses, then NIVO 240 mg Q2W), or chemo. Dual primary endpoints were OS and PFS (per blinded independent central review) in pts with PD-L1 combined positive score (CPS) ≥ 5 for NIVO + chemo vs chemo. Hierarchically tested secondary endpoints included OS in NIVO + chemo vs chemo (PD-L1 CPS ≥ 1, then all randomized). Results: Of 2031 pts, 1581 were randomized to NIVO + chemo or chemo. In all randomized pts, 41% of pts (NIVO + chemo) and 44% of pts (chemo) received subsequent therapy. Median PFS2 (time from randomization to progression after subsequent systemic therapy, initiation of second subsequent systemic therapy, or death, whichever is earlier) was 12.2 (95% CI 11.3–13.5) mo with NIVO + chemo and 10.4 (95% CI 9.7–11.2) mo with chemo (HR 0.75 [95% CI 0.67–0.84]). 51% of pts (NIVO + chemo) and 43% of pts (chemo) had > 50% reduction from baseline in tumor burden, while 24% and 17% had > 80% reduction, respectively. The HR (95% CI) for OS was 0.66 (0.56–0.77) among pts with a PD-L1 CPS ≥ 10 (median OS for NIVO + chemo vs chemo: 15.0 [95% CI 13.7–16.7] vs 10.9 [95% CI 9.8–11.9] mo). OS benefit was observed with NIVO + chemo vs chemo across multiple additional subgroups, and these data will be presented. No new safety signals were identified. The majority of the treatment-related adverse events with potential immunologic etiology were grade 1 or 2 and grade 3 or 4 events were reported in ≤ 5% of pts in both treatment arms. Conclusions: NIVO + chemo continued to demonstrate clinically meaningful efficacy and an acceptable safety profile with longer follow-up, further supporting the use of NIVO + chemo as a standard 1L therapy in previously untreated pts with advanced GC/GEJC/EAC. Clinical trial information: NCT02872116.
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 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,003 | 0,001 |
| 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 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 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 ».