Reanalysis of Urothelial Cancer Chemoimmunotherapy Trials With Differential Censoring
Notice bibliographique
Résumé
Importance: Three similar phase 3 randomized clinical trials have investigated PD-1/PD-L1 (programmed cell death 1 protein/programmed cell death 1 ligand 1) inhibitors in combination with platinum-based chemotherapy vs chemotherapy alone as first-line treatment for advanced urothelial carcinoma (IMvigor130, atezolizumab; KEYNOTE-361, pembrolizumab; and CheckMate901, nivolumab). Only CheckMate901 reported overall survival (OS) benefit for the combination. The reason for these inconsistent results is unclear. Objective: To explore whether differential censoring-that is, censoring imbalance between the study groups-is a possible explanation for these inconsistent findings. Design, Setting, and Participants: This comparative effectiveness study involved a censoring analysis of data from IMvigor130, KEYNOTE-361, and CheckMate901, which enrolled patients between 2016 and 2022. Participants included patients in these 3 trials. Exposure: Participation in 1 of the 3 trials. Main Outcomes and Measures: The primary outcomes were censoring rates adjusted for treatment effects. Censoring rates were calculated from the Kaplan-Meier (KM) curves. When excess censoring in the control group of open-label trials was found, the hypothesis was that better-performing patients might be dropping out to seek alternative treatments; a sensitivity analysis was conducted in which their survival was assumed to be similar to that of the longest surviving patients in the control group. Treatment effects of the censoring-adjusted KM curves were calculated using the 2-sided log-rank test. Results: The 3 trials involved a total of 2162 patients (1640 male [76%]; age range, 65-69 years) Analysis of progression-free survival (PFS) curves demonstrated no differential censoring in IMvigor130, but there was more than 30% excess censoring in the chemotherapy-only groups in KEYNOTE-361 and CheckMate901 trials. After sensitivity analysis, the PFS benefit was no longer significant in either study (KEYNOTE-361, adjusted hazard ratio [HR], 1.13 [95% CI, 0.95-1.35]; CheckMate901, adjusted HR, 1.17 [0.96-1.44]). Analysis of OS curves demonstrated no differential censoring in IMvigor130 or KEYNOTE-361, but there was more censoring in the chemotherapy-only group in CheckMate901. After sensitivity analysis, the OS benefit of adding nivolumab to chemotherapy was lost (before adjustment, HR, 0.77 [95% CI, 0.63-0.95]; P = .01; adjusted HR, 0.95 [95% CI, 0.77-1.17]; P = .64). Conclusions and Relevance: In this comparative effectiveness study, differential censoring explained the inconsistent results reported in the evaluated trials. The term perceived-inferiority censoring is suggested to describe a phenomenon wherein better-performing patients are aware of their treatment and drop out to pursue alternative therapeutic options; it is possible that this occurred in the open-label KEYNOTE-361 and CheckMate901 trials. Such censoring confounds randomization and interpretation of clinical trials, since a larger experimental group is compared with a selected group of controls with poorer prognosis.
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) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 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) | 0,001 | 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 ».