1L pembrolizumab (pembro) versus chemotherapy (chemo) for choice-of-carboplatin patients with advanced urothelial carcinoma (UC) in KEYNOTE-361.
Notice bibliographique
Résumé
450 Background: 1L pembro is approved in advanced UC for cisplatin-ineligible pts with PD-L1 combined positive score (CPS) ≥10 and any platinum-ineligible pts regardless of CPS in the United States based on single-arm trial data. In the phase III KEYNOTE-361 study, 1L pembro + chemo did not statistically significantly improve PFS or OS vs chemo for pts with advanced UC; formal testing of 1L pembro vs chemo was not performed. We present an exploratory analysis of outcomes with pembro vs chemo for choice-of-carboplatin (carbo) pts in KEYNOTE-361 (NCT02853305). Methods: At randomization, choice of platinum agent (cisplatin or carbo) plus gemcitabine for each pt was selected based on investigator’s assessment of cisplatin ineligibility. ORR/DOR per RECIST v1.1 by blinded independent central review and OS were determined for all pts selected for carbo (“choice-of-carbo”) and also choice-of-carbo pts with CPS ≥10. Risk difference assessment for select AEs for pembro vs chemo was conducted in choice-of-carbo pts who received ≥1 dose study treatment. Results: As of Apr 29, 2020, the median (range) time from randomization to data cutoff in the full study cohort was 31.7 (22.0-42.3) mo. At randomization, renal impairment was the most common reason for choice of carbo by investigators (36% of all pts). 170 choice-of-carbo pts were randomized to the pembro arm, and 196 choice-of-carbo pts to the chemo arm. Median OS in this subgroup was 14.6 mo with pembro vs 12.3 mo with chemo (HR 0.83 [95% CI 0.65-1.06]). 18-mo OS rate was 42% with pembro vs 40% with chemo. ORR to pembro vs chemo was 27.6% vs 41.8%. Median (range) DOR with pembro vs chemo was not reached (NR) (3.2+-36.1+ mo) vs 6.3 (1.8+-33.8+) mo. 84/170 (49%) and 89/196 (45%) choice-of-carbo pts in the pembro and chemo arms, respectively, had CPS ≥10. In this subgroup, median OS was 15.6 mo with pembro vs 13.5 mo with chemo (HR 0.82 [95% CI 0.57-1.17]). 18-mo OS rate was 44% with pembro vs 43% with chemo. ORR to pembro vs chemo was 29.8% vs 46.1%. Median (range) DOR with pembro vs chemo was NR (4.2-36.1+ mo) vs 8.3 (2.1+-33.8+) mo. Among treated pts (N=166 for pembro, N=190 for chemo), 112 pts (68%) in the pembro arm and 163 pts (86%) in the chemo arm had grade 3-5 AEs of any cause. Pembro was associated with a higher risk of pruritus, while chemo was associated with a higher risk of decreased white blood cell, neutrophil, and platelet counts, nausea, thrombocytopenia, neutropenia, and anemia. Conclusions: Due to the trial design, this subset was not statistically tested and is exploratory. Median OS and 18-mo OS rates did not appear markedly different in the two arms; some parameters such as DOR favored pembro, although longer follow-up is needed to determine median DOR for pembro. The PD-L1 CPS ≥10 did not clearly enrich for responders to pembro in choice-of-carbo pts. Pembro was associated with a lower rate of grade 3-5 AEs of any cause than chemo. Clinical trial information: NCT02853305.
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 | 0,003 | 0,003 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,002 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,001 | 0,001 |
| Intégrité de la recherche | 0,001 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,007 | 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 ».