Abstract PD4-04: Updated results of tucatinib vs placebo added to trastuzumab and capecitabine for patients with previously treated HER2-positive metastatic breast cancer with brain metastases (HER2CLIMB)
Notice bibliographique
Résumé
Abstract Background: Tucatinib is an oral tyrosine kinase inhibitor highly specific for HER2 that is approved for use in combination with trastuzumab and capecitabine in adults with advanced or metastatic HER2+ breast cancer, including patients with brain metastases, who have received one or more prior anti-HER2-based regimens in the metastatic setting. In the HER2CLIMB trial, the tucatinib regimen significantly prolonged progression-free survival (PFS) and overall survival (OS) in patients with HER2+ metastatic breast cancer (Murthy, NEJM 2020), including in patients with untreated, treated stable, and treated progressing brain metastases (Lin, J Clin Oncol, 2020). With an additional 15.6 months of follow-up, addition of tucatinib continued to show clinically meaningful prolongation of PFS and OS in the total study population (Curigliano, ASCO Meeting, 2021). We report updated results of exploratory efficacy analyses in patients with brain metastases. Methods: All patients in HER2CLIMB had a baseline brain MRI. Patients with brain metastases were eligible and classified as untreated, treated stable, or treated progressing. Patients were randomized 2:1 to receive tucatinib 300 mg twice daily or placebo, in combination with trastuzumab and capecitabine. Following the primary analysis, the protocol was amended to unblind sites to treatment assignment and allowed crossover from the placebo regimen to the tucatinib regimen. Efficacy analyses in patients with brain metastases at baseline were performed at approximately 2 years from the last patient randomized by applying RECIST 1.1 to the brain based on investigator evaluation. OS and CNS-PFS (progression in the brain or death) were evaluated in all patients with brain metastases. Patients without CNS-PFS events were censored at the last brain MRI. Confirmed intracranial (IC) objective response rate (ORR-IC) was evaluated in patients with measurable IC disease. Results: At a median follow-up of 29.6 months, median OS was 21.6 months vs 12.5 months in all patients with brain metastases (HR: 0.60; 95% CI: 0.44, 0.81), 21.4 months vs 11.8 months in patients with untreated/treated progressing brain metastases (HR: 0.52; 95% CI: 0.36, 0.77), and 21.6 months vs 16.4 months in patients with treated stable brain metastases (HR: 0.70; 95% CI: 0.42, 1.16). Median CNS-PFS was 9.9 months vs 4.2 months in all patients with brain metastases (HR: 0.39; 95% CI: 0.27, 0.56), 9.6 months vs 4.0 months in patients with untreated/treated progressing brain metastases (HR: 0.34; 95% CI: 0.22, 0.54), and 13.9 months vs 5.6 months in patients with treated stable brain metastases (HR: 0.41; 95% CI: 0.19, 0.85). ORR-IC was higher in the tucatinib arm (47.3%; 95% CI: 33.7, 61.2) vs the placebo arm (20.0%; 95% CI: 5.7, 43.7) for patients with brain metastases, and median duration of response (DOR) was 8.6 months (95% CI: 5.5, 10.3) vs 3.0 months (95% CI: 3.0, 10.3). Conclusions: With 15.6 months of additional follow-up, the tucatinib-trastuzumab-capecitabine regimen resulted in a robust and durable prolongation of OS for all patients with HER2+ metastatic breast cancer and brain metastases. Additionally, this benefit was maintained in patients with untreated/treated progressing and treated stable brain metastases. Treatment with tucatinib continued to show clinically meaningful benefit in CNS-PFS consistent with the primary analysis. Citation Format: Nancy U Lin, Rashmi K Murthy, Vandana Abramson, Carey Anders, Thomas Bachelot, Philippe Bedard, Virginia Borges, David Cameron, David Cameron, Lisa Carey, A Jo Chien, Giuseppe Curigliano, Michael DiGiovanna, Karen Gelmon, Gabriel Hortobagyi, Sara Hurvitz, Ian Krop, Sherene Loi, Sibylle Loibl, Volkmar Mueller, Mafalda Oliveira, Elisavet Paplomata, Mark Pegram, Dennis Slamon, Amelia Zelnak, Jorge Ramos, Wentao Feng, Eric Winer. Updated results of tucatinib vs placebo added to trastuzumab and capecitabine for patients with previously treated HER2-positive metastatic breast cancer with brain metastases (HER2CLIMB) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD4-04.
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 distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 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 tête enseignante, 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 ».