Abstract RF02-01: A Multicenter, Phase I/II Trial of Anastrozole, Palbociclib, Trastuzumab, and Pertuzumab in Hormone Receptor (HR)-Positive, HER2-Positive Metastatic Breast Cancer (ASPIRE)
Notice bibliographique
Résumé
Abstract Background: Among patients (pts) with HR-positive and HER2-positive breast cancer, crosstalk between HER2 and estrogen receptor (ER) signaling pathways may contribute to endocrine resistance but anti-HER2 agents in combination with endocrine therapy can restore endocrine sensitivity. Mechanistically, HER2/HER3 signaling promotes survival by way of PI3K-AKT activation whereas ER-CDK4/6-Rb signaling promotes cell cycle progression. The combination of anti-HER2 therapy with an aromatase inhibitor (AI) and a CDK 4/6 inhibitor would allow for blockade of both pathways and provide a novel, all biologic, and chemotherapy-free approach to the treatment of HR-positive, HER2-positive metastatic breast cancer (MBC). Methods: We conducted a phase I/II multi-institution trial in pts with previously untreated, HR-positive and HER2-positive MBC. In the Phase I portion, pts received escalating doses of palbociclib (100mg, 125mg) in conjunction with trastuzumab, pertuzumab and an AI anastrozole, using a 3+3 dose escalation trial design. In the phase II portion, pts received palbociclib at the maximum tolerated dose (MTD), anastrozole, trastuzumab, and pertuzumab. The primary endpoints of the Phase I and II portions were MTD and clinical benefit rate (CBR) defined as the sum of complete response, partial response, and stable disease for >/= 6 months, respectively. Secondary endpoints included progression free survival (PFS), objective response rate (ORR) and safety. The Phase II portion of this study was powered with 30 pts to show efficacy of palbociclib administered at the MTD in combination with anastrozole, trastuzumab and pertuzumab if the CBR achieved at 6 months exceeded 58%. The Clopper-Pearson method was used to calculate confidence intervals for ORR and CBR. The PFS distribution was estimated using the Kaplan-Meier method. Results: In the Phase I portion, a total of 9 pts were enrolled. No DLTs were observed at the 100mg dose (N=3) or the 125mg dose (N=6) level, and thus, 125mg was established as the MTD. An additional 24 pts were enrolled to the Phase II portion at the MTD, with a total of 30 pts in the modified intention-to-treat population included in the efficacy analysis. The median age of the population was 57.6 years (range 50.5-63.8) and 27% of pts were premenopausal and received ovarian function suppression as part of treatment. As shown in Table 1, the primary endpoint, CBR, was 97% (95% CI: 0.83-1.0, p<0.0001). ORR was 70% (95% CI: 0.51-0.85). Median time to objective response was 2.8 months with earliest response at 3 months. Median duration of response was not reached with range of 5.1-42.2 months. Median PFS was also not reached with range of 8-44.8 months. Safety data were consistent with known toxicity profiles of agents. Most common adverse events included diarrhea (80%), neutropenia (77%), leukopenia (70%), anemia (67%), and fatigue (60%). Grade 3-4 events occurred in 63% (19/30) of pts and included neutropenia (68%), leukopenia (32%), decrease in absolute neutrophil count (21%), and anemia (21%). Conclusions: The combination of anastrozole, palbociclib, trastuzumab, and pertuzumab was well tolerated and effective with a clinical benefit rate of 97% in pts with previously untreated HR-positive, HER2-positive MBC. The combination provides a chemotherapy-free alternative for pts with triple positive breast cancers. Further follow up will determine impact on PFS. Table 1. Results in Patients on Anastrozole, Palbociclib, Trastuzumab, and Pertuzumab Citation Format: Rima Patel, Krystal Cascetta, Paula Klein, Erin Moshier, Maryann Kwa, Julie Fasano, Anupama Goel, Melissa Accordino, Charles Shapiro, Rita Vaccaro, Gargi Atul Joshi, Joseph Sparano, Amy Tiersten. A Multicenter, Phase I/II Trial of Anastrozole, Palbociclib, Trastuzumab, and Pertuzumab in Hormone Receptor (HR)-Positive, HER2-Positive Metastatic Breast Cancer (ASPIRE) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr RF02-01.
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 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 | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| 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 ».