Comparable efficacy and safety of taletrectinib for advanced ROS1+ non–small cell lung cancer across pivotal studies and between races and world regions.
Notice bibliographique
Résumé
8643 Background: Taletrectinib is a highly potent, next-generation, central nervous system–active, selective ROS1 tyrosine kinase inhibitor (TKI) that was evaluated in 2 pivotal ROS1+ non–small cell lung cancer (NSCLC) phase 2 trials: the regional TRUST-I (NCT04395677) and global TRUST-II (NCT04919811) studies. While earlier trials suggest its safety and efficacy data are consistent across racial and geographic factors, further analysis is required to confirm the consistency of outcomes and applicability of results across regions. Here, we compare the efficacy and safety of taletrectinib within and between the pivotal regional TRUST-I and global TRUST-II studies through predefined subgroup analyses. Methods: The pivotal cohorts of TRUST-I (N=173) and TRUST-II (N=159) had similar study designs, which included the same primary endpoint (confirmed objective response rate [cORR] by independent review committee per RECIST v1.1) and secondary endpoints, as well as similar inclusion/exclusion criteria and safety evaluation methods. Key efficacy and safety profiles were compared in 3 ways: (a) between TRUST-I and TRUST-II, (b) across Western (North America and Europe) and Asian regions, and racial subgroups, in the pooled study population of TRUST-I and TRUST-II, and (c) between Western and Asian regions and other subgroups in the global TRUST-II study. Relative risk (RR) and associated 95% confidence intervals (CIs) via the Wald method were used to compare data (data cutoff June 2024). Results: When comparing TRUST-I and TRUST-II, cORRs were consistent for TKI-naive (91% vs 85%; RR: 0.94 [95% CI: 0.83, 1.07]) and TKI-pretreated pts (52% vs 62%; RR: 1.20 [95% CI: 0.87, 1.66]). Rates of grade ≥3 treatment-emergent adverse events (TEAEs) were consistent across both studies (51% vs 51%, RR: 1.0 [95% CI: 0.81, 1.24]). TEAEs leading to dose interruptions (41% vs 40%) and discontinuations (6% vs 8%) were similar. In subgroup analyses of the pooled patient population by race, Asian and non-Asian patients had similar cORRs in both TKI-naive (89% vs 84%; RR: 0.94 [95% CI: 0.77, 1.15]) and TKI-pretreated (52% vs 68%; RR: 1.30 [95% CI: 0.93, 1.82]) groups. Comparison of different efficacy and safety profiles among subgroups in the pooled data set also showed consistency among races and regions. Within the multiregional TRUST-II study, cORRs were high in TKI-naive patients regardless of region (Western: 81%; Asia: 88%), prior chemotherapy (yes: 90%; no: 84%), and race (White: 83%; Asian: 86%; other: 86%). Similarly, major safety profiles were comparable between Asian and Western patients and between races within TRUST-II. Conclusions: Taletrectinib showed comparable efficacy and safety that were not impacted by geographic and racial factors. Therefore, the clinical benefit of taletrectinib is broadly applicable to ROS1+ NSCLC patients globally. Clinical trial information: NCT04395677 , NCT04919811 .
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 | 0,014 | 0,012 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,004 |
| Bibliométrie | 0,001 | 0,001 |
| 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 | 0,001 |
| 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 ».