Abstract P4-14-01: Trastuzumab emtansine improves overall survival versus capecitabine plus lapatinib in patients with previously treated HER2-positive advanced breast cancer: Final results from the phase 3 EMILIA study
Notice bibliographique
Résumé
Abstract Introduction T-DM1 is indicated for the treatment of advanced HER2-positive MBC in patients who previously received trastuzumab and a taxane (separately or in combination) based on data from the phase 3 EMILIA study (BO21977/TDM4370g; NCT00829166). In the primary PFS and second interim OS analyses, respectively, T-DM1 significantly improved PFS (median 9.6 vs 6.4 months; HR=0.65; 95% CI, 0.55–0.77; p<0.0001) and OS (median 30.9 vs 25.1 months; HR=0.68; 95% CI, 0.55–0.85; p<0.0006) compared with capecitabine (X) plus lapatinib (L). T-DM1 treatment was associated with fewer grade ≥3 AEs (41% vs 57%) vs XL. Here we present the final OS analysis from EMILIA. Methods EMILIA was a randomized, open-label study of patients with centrally confirmed HER2-positive (IHC3+ and/or FISH amplification ratio ≥2.0), unresectable, locally advanced or MBC, previously treated with trastuzumab and a taxane. Patients were randomized 1:1 to T-DM1 (3.6 mg/kg IV every 3 weeks) or X (1000 mg/m2 PO twice daily, days 1–14 every 3 weeks) plus L (1250 mg PO daily). The final OS analysis was to be conducted following 632 events, and these results are descriptive only. Since the OS efficacy boundary (HR<0.71, p=0.0025) was crossed in the second interim analysis, a protocol amendment allowed crossover from XL to T-DM1. Results From Feb 2009 to Oct 2011, 991 patients were randomized to T-DM1 (n=495) or XL (n=496). Patient disposition by the data cutoff (31 Dec 2014) is shown in Table 1. OS was longer with T-DM1 vs XL (median OS 29.9 vs 25.9 months; HR=0.75; 95% CI, 0.64–0.88; p=0.0003). In a sensitivity analysis, which censored crossover patients at the time of switching from XL to T-DM1, the HR was 0.69 (95% CI, 0.59–0.82; p<0.0001). The overall safety profile was similar to previous analyses (Table 2). More grade ≥3 thrombocytopenia occurred with T-DM1 vs XL (14.3% vs 0.4%). Cardiac dysfunction occurred in 2.7% of T-DM1 patients vs 3.5% of XL patients. Table 1. Patient disposition. T-DM1 (n=495)XL (n=496)Median treatment duration, months7.6X: 5.3 L: 5.5Median duration of follow-up, months47.841.9Discontinued study, n (%)364 (74)404 (82)Crossover, n (%) Per protocolaNot applicable136 (27)Non-protocol therapybX: 252 (54)X: 53 (11) L: 224 (48)L: 74 (15)aMedian duration of follow-up among per-protocol crossover patients was 24.1 months.bBy investigator choice after study treatment discontinuation; X or L could be given in combination with each other or other agents after progression. Table 2. Safety summary in patients who received ≥1 dose of study treatment.n (%)T-DM1 (n=490)XL (n=488)Grade ≥3 AEs233 (47.6)291 (59.6)Serious AEs91 (18.6)99 (20.3)AEs leading to dose reduction91 (18.6)X: 205 (42.0) L: 98 (20.1) Conclusions This final analysis of EMILIA shows an OS benefit of T-DM1 compared with XL. While median drug exposure was longer with T-DM1 than XL, T-DM1 was associated with fewer grade ≥3 AEs and AEs leading to dose reduction compared with XL. These final OS results confirm that T-DM1 treatment improved survival, even in the presence of treatment crossover, and reaffirm T-DM1 as the standard of care in patients with previously treated HER2-positive MBC. Citation Format: Diéras V, Miles D, Verma S, Pegram M, Welslau M, Baselga J, Krop I, Blackwell K, Kang B, Xu J, Green M, Gianni L. Trastuzumab emtansine improves overall survival versus capecitabine plus lapatinib in patients with previously treated HER2-positive advanced breast cancer: Final results from the phase 3 EMILIA study. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-14-01.
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) | 0,002 | 0,003 |
| 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 ».