Abstract OT2-07-03: Trastuzumab deruxtecan (DS-8201a) vs ado-trastuzumab emtansine (T-DM1) for subjects with HER2-positive, unresectable and/or metastatic breast cancer who previously received trastuzumab and a taxane: A phase 3, randomized study
Notice bibliographique
Résumé
Abstract Background: Ado-trastuzumab emtansine (T-DM1), a HER2-targeted antibody drug conjugate (ADC), is approved for patients with HER2-positive metastatic breast cancer (BC) after disease progression on a trastuzumab-based regimen. Approval of T-DM1 was based on the EMILIA trial in which T-DM1 demonstrated an objective response rate (ORR) of 43.6%, a median progression-free survival (PFS) of 9.6 months, and an overall survival (OS) of 30.9 months (Verma S, et al. NEJM. 2012). DS-8201a is a novel HER2-targeted ADC with a humanized HER2 antibody attached to a topoisomerase I inhibitor payload by a cleavable peptide-based linker, and with a high drug-to-antibody ratio of 7 to 8. In an ongoing phase 1 trial, DS-8201a showed a manageable safety profile and promising antitumor activity in HER2-positive BC previously treated with T-DM1 (confirmed ORR of 54.5%; April 2018 data cutoff) (Iwata et al, ASCO 2018). The pivotal, phase 2 DESTINY-BREAST01 trial in this population with HER2-positive BC who received prior T-DM1 is ongoing (Baselga et al, ASCO 2018). Study Description: This multicenter, open-label, phase 3 trial will assess the efficacy and safety of DS-8201a vs T-DM1 in subjects with HER2-positive (IHC 3+ or IHC 2+/ISH+; confirmed by centralized testing) unresectable and/or metastatic BC previously treated with trastuzumab and a taxane (NCT03529110, DESTINY-BREAST03). Subjects who previously received a HER2-targeted ADC are excluded. Approximately 500 eligible subjects will be randomized (1:1) to receive DS-8201a (5.4 mg/kg) or T-DM1 (3.6 mg/kg) IV once every 3 weeks. Randomization will be stratified by hormone receptor status, prior pertuzumab treatment, and history of visceral disease. For subjects randomized to T-DM1, the treatment will be in accordance with the approved label. The primary efficacy endpoint is PFS based on blinded, independent central review using RECIST v1.1 criteria. Secondary efficacy endpoints include OS, ORR, duration of response, clinical benefit rate, and PFS based on investigator assessment. Safety assessments include serious and treatment-emergent adverse events, physical examinations, vital signs, and clinical laboratory parameters. Health related quality of life will also be measured. The primary analysis for PFS will be performed when approximately 331 PFS events have been observed. This will provide 90% power to detect a hazard ratio of 0.70 for PFS with a 1-sided alpha of 0.025, assuming a median PFS with T-DM1 of 9.6 months and that PFS follows an exponential distribution. Long-term follow-up will continue after the primary analysis every 3 months until death, withdrawal of consent, loss to follow-up, or study closure. Efficacy analyses will include all randomized subjects, and safety analyses will include all randomized subjects who received ≥1 dose of study treatment. The study will enroll subjects from approximately 150 sites851468 including in North America, Europe, and Asia. Citation Format: Verma S, Shahidi J, Lee C, Wang K, Cortes J. Trastuzumab deruxtecan (DS-8201a) vs ado-trastuzumab emtansine (T-DM1) for subjects with HER2-positive, unresectable and/or metastatic breast cancer who previously received trastuzumab and a taxane: A phase 3, randomized study [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT2-07-03.
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) | 0,002 | 0,001 |
| Méta-épidémiologie (sens large) | 0,002 | 0,002 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,002 | 0,001 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,002 | 0,004 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,010 | 0,002 |
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 ».