Overall survival in patients who received checkpoint inhibitors after completing tebentafusp in a phase 3 randomized trial of first-line metastatic uveal melanoma.
Notice bibliographique
Résumé
9526 Background: Tebentafusp (tebe) is a bispecific consisting of an affinity-enhanced T cell receptor fused to an anti-CD3 effector that can redirect T cells to target gp100+ cells. Tebe significantly improved OS compared to investigator’s choice (IC) in first line (1L) mUM [NCT03070392]. In a phase (ph) 2 study of tebe in 2L+ mUM (NCT02570308), several checkpoint inhibitor (CPI) refractory pts who were retreated with CPI after tebe achieved durable clinical benefit [1]. We therefore evaluated clinical outcomes of post-tebe CPI in patients treated on the ph3 trial of tebe versus investigator’s choice (IC) [NCT03070392]. Methods: In the ph3 trial, 378 HLA-A*02:01+ 1L mUM pts were randomized 2:1 to tebe (n=252) or IC (n=126) [pembrolizumab (82%), ipilimumab (12%) or dacarbazine (6%)]. No crossover to tebe was permitted, investigators were free to choose subsequent therapy, and there was no re-randomization at time of subsequent therapy. This analysis was conducted on the first interim analysis (data extracted Nov-2020). When pts received more than one subsequent therapy, the first was used in these analyses. Medians and 1-yr OS from the start of post-study therapy are obtained from standard Kaplan-Meier analyses; hazard ratios (HR) are from Cox regression models adjusted for age and gender. Results: 106/252 (42%) tebe pts received ≥ 1 subsequent therapy: 35% CPI, 9% chemo, 6% liver directed therapy (LDT), 6% other. 55/126 (44%) of IC pts received ≥ 1 subsequent therapy: 21% CPI, 10% chemo, 12% LDT, 10% other. Median time to first subsequent therapy was longer for tebe pts at 5.2 mo vs. IC pts at 3.8 mo. The median duration from start of first subsequent CPI to end date was longer in the prior tebe pts at 4 mo vs prior IC pts at 2.8 mo. From the start of any first subsequent therapy, prior tebe pts had longer OS compared to prior IC pts, HR 0.67 (95% CI 0.42, 1.07). Most of the subsequent therapy was CPI, and the OS benefit was also seen in this subset, HR 0.62 (95% CI 0.34, 1.14). For prior tebe pts, the median and 1-yr OS rates from start of any first subsequent therapy were 13 mo and 53% and from start of first subsequent CPI were 16 mo and 63%. Both were higher than the sequence of IC followed by any therapy (11 mo and 44%), IC followed by CPI (9 mo and 47%) and a recent meta-analysis of 2L+ mUM (7 mo and ̃35% 1-yr OS rate). Conclusions: Pts who progressed on tebe and then received CPI had better OS compared to pts who progressed on IC and then received CPI. Further analysis will explore whether confounding factors are influencing this effect. These exploratory data suggest that tebe, relative to IC, may improve outcomes to subsequent CPI. (1)Yang J. et al. ASCO 2019, J . Cli n Oncol 37:15_suppl, 9592. Clinical trial information: NCT03070392.
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 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,001 |
| Méta-épidémiologie (sens large) | 0,002 | 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 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,003 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,004 | 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 ».