Post hoc analysis of the efficacy of pembrolizumab retreatment after progression of advanced urothelial carcinoma (UC) in KEYNOTE-045 and KEYNOTE-052.
Notice bibliographique
Résumé
512 Background: Pembrolizumab (pembro) has shown efficacy in advanced/unresectable and metastatic UC (mUC). There is interest in determining whether pts should be treated subsequently with checkpoint inhibitors such as anti–PD-1 therapy if mUC responds then later progresses. Pembro retreatment after disease progression has shown efficacy in melanoma and NSCLC. This post hoc exploratory analysis investigated the efficacy of pembro retreatment for pts with advanced UC or mUC enrolled in KEYNOTE-045 and KEYNOTE-052 with a best overall response (BOR) of SD or better and whose disease progressed after discontinuation or completion of 2 y of therapy. Methods: The phase 3 KEYNOTE-045 trial (NCT02256436) was designed to compare the efficacy and safety of pembro vs chemotherapy (chemo) in pts with mUC that recurred/progressed on platinum containing chemo; ≤2 prior lines of systemic chemo for mUC were permitted. The phase 2 KEYNOTE-052 trial (NCT02335424) was designed to evaluate the efficacy and safety of first-line pembro in cisplatin-ineligible pts with advanced UC. In both studies, pembro was administered for up to 2 y; pts were eligible for retreatment if they stopped pembro after CR or had a BOR of CR, PR, or SD and completed 2 y of treatment. Pts must have investigator-confirmed radiographic PD after therapy cessation, have ECOG PS score 0-1, and not have received anticancer treatment after the last pembro dose. BOR to retreatment is reported. Results: At data cutoff for KEYNOTE-045 (Oct 1, 2020), 11 pts were retreated: 5 (45%) achieved objective response to retreatment (3 CR; 2 PR; Table) and 6 had SD, for a disease control rate (DCR; CR+PR+SD) of 100%. Median treatment-free interval was 7.7 mo (IQR, 3.6-16.5); median duration of retreatment was 11.4 mo (IQR, 7.6-12.0). Seven pts (64%) were alive at cutoff. At data cutoff for KEYNOTE-052 (Sep 26, 2020), 10 pts were retreated; 5 (50%) had objective response to retreatment (1 CR; 4 PR) and 4 had SD, for a DCR of 90%. Retreatment BOR was PD for 1 pt (10%). Median treatment-free interval was 13.0 mo (9.2-16.6); median duration of retreatment was 6.0 mo (IQR, 4.9-9.2). Four pts (40%) were alive at cutoff. Conclusions: Although the number of pts who received retreatment was small, objective responses were observed. The findings are generally consistent with observations from retreatment in other tumor types (e.g., melanoma). Clinical trial information: NCT02256436 and NCT02335424. [Table: see text]
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 | 0,015 | 0,017 |
| Méta-épidémiologie (sens strict) | 0,002 | 0,001 |
| Méta-épidémiologie (sens large) | 0,004 | 0,006 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,001 | 0,002 |
| Science ouverte | 0,002 | 0,001 |
| Intégrité de la recherche | 0,002 | 0,005 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,011 | 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 ».