Enfortumab vedotin (EV) with pembrolizumab (P) versus chemotherapy (chemo) in previously untreated locally advanced or metastatic urothelial carcinoma (la/mUC): Analysis of the cisplatin (cis)-ineligible population from EV-302/KEYNOTE-A39.
Notice bibliographique
Résumé
4563 Background: EV-302/KEYNOTE-A39 (NCT04223856) is a phase 3, randomized, open-label, global study comparing EV+P with platinum-based chemo (PBC) for first-line (1L) treatment (tx) of patients (pts) with la/mUC regardless of cis eligibility. In EV-302, EV+P demonstrated a statistically significant and clinically meaningful benefit compared with PBC for the dual primary endpoints of PFS (hazard ratio [HR]: 0.45; P<0.00001) and OS (HR: 0.47; P<0.00001) in the overall pt population (Powles ESMO 2023), reducing the risk of progression and/or death by more than 50%. EV+P was FDA-approved in Dec 2023 for tx of adults with la/mUC. As cis eligibility status has long defined 1L tx, here we present results of an analysis for pts who were ineligible for cis at randomization. Methods: Pts with previously untreated la/mUC were randomized 1:1 to receive 3-week cycles of EV (1.25 mg/kg IV; Days 1 and 8) and P (200 mg IV; Day 1) or PBC (gemcitabine with cis or carboplatin [carbo]). Select secondary endpoints included confirmed objective response rate (ORR), duration of response (DOR), and safety. Pts were deemed eligible/ineligible for cis following protocol-defined criteria and stratified accordingly. Results: 408 pts (EV+P: 198, PBC: 210) were cis-ineligible at randomization. 205 (97.6%) pts in the PBC arm received carbo at Cyle 1. mPFS was 10.6 months for EV+P; 6.1 months for PBC (HR: 0.43, 95% CI, 0.33, 0.55). mOS was not reached for EV+P and was 12.7 months for PBC (HR: 0.43, 95% CI, 0.31, 0.59). ORR for EV+P was 63.9% with 24.7% complete response (CR) rate; mDOR (95% CI) was not reached (16.3 months, NR). ORR for PBC was 34.9% with 9.1% CR rate; mDOR (95% CI) was 6.6 months (5.6, 10.2). In EV+P arm, 62 pts (31.3%) remained on tx at data cutoff (DCO). 55 pts (27.8%) received subsequent therapy. 10 pts received cis and 27 pts received carbo as first subsequent therapy. In PBC arm, all were off study tx at DCO. 114 pts (54.3%) received any PD-1/L1 therapy following PBC. 52 pts received maintenance avelumab; 58 pts received PD-1/L1 therapy as second-line tx. Grade ≥3 TRAEs occurred in 58.4% of pts with EV+P and 77.1% of pts with PBC. Most common grade ≥3 TRAEs of special interest for EV were skin reactions (16.2%), peripheral neuropathy (8.1%), and hyperglycemia (4.1%). Most common grade ≥3 tx-emergent AEs of special interest for P were severe skin reaction (14.7%), hepatitis (2.0%), and pneumonitis (2.0%). Conclusions: In this pt population with historically poor prognosis, EV+P improved clinical outcomes in pts who were ineligible for cis; results were consistent with the overall population. The risk of death was reduced by more than 50%. The AE profile of EV+P was generally manageable with no new safety signals. The results of EV-302 support EV+P as a new SOC for la/mUC, including pts who are ineligible for cis. Clinical trial information: NCT04223856 .
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 | 0,002 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| 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 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 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 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 ».