A phase 1 study of abemaciclib and niraparib as neoadjuvant therapy in hormone receptor positive and HER2 negative breast cancer.
Notice bibliographique
Résumé
e12598 Background: Less than 20% of hormone receptor-positive HER2-negative breast cancer (HRBC) patients (pts) achieve pathologic complete response with current chemotherapy-based neoadjuvant treatment (NAT). There is a need to evaluate novel non-chemotherapy NAT regimens for HRBC. Abemaciclib is a cyclin dependent kinase 4/6 inhibitor approved for the treatment of high-risk early stage and metastatic HRBC. Niraparib is a poly-ADP-ribose polymerase inhibitor (PARPi) approved for the treatment of ovarian cancers. In preclinical data, treatment with abemaciclib sensitizes tumors to DNA damaging agents such as PARPi. This is a phase 1 study evaluating the combination of abemaciclib and niraparib as NAT for HRBC (NCT04481113). Methods: Pts aged ≥18 years with biopsy-proven stage I-III HRBC (ER ≥1%, PR ≥1%, HER2 non-amplified) planned for NAT were eligible for this study. Pts were treated according to a traditional 3+3 dose-escalation algorithm, with the starting dose level 1 (DL1) consisting of abemaciclib 150 mg PO BID and niraparib 100 mg PO daily, and DL2 of abemaciclib 150 mg PO BID and niraparib 200 mg PO daily. After 2 cycles, pts underwent repeat imaging and biopsy. Pts with response or stable disease (SD) received an additional 2 cycles of treatment, while pts with progressive disease (PD) were switched to standard of care chemotherapy. The primary endpoints were to determine the maximum-tolerated dose (MTD) and incidence of dose-limiting toxicities (DLTs). Results: A total of 8 pts were enrolled. Median age was 56 years, 6 were postmenopausal and 2 premenopausal. No pts had germline BRCA mutations. No DLTs occurred among 3 pts treated at DL1; however, 2 DLTs occurred at DL2, including one hematological DLT (dose delay >7 days due to myelosuppression) and a grade 5 cardiac adverse event (AE). Most AEs were grade 1-2, with the most common being gastrointestinal toxicities. The study was subsequently closed to accrual. The MTD was determined to be abemaciclib 150 mg PO BID and niraparib 100 mg PO daily. Among 5 pts who completed 2 cycles of abemaciclib and niraparib followed by disease evaluation, 2 achieved a partial response and 3 had SD by modified RECIST. There was no PD noted on study therapy. No locoregional or distant recurrences were noted at 3-year follow up. Serial biopsies on trial demonstrated tumor heterogeneity, and 2 pts with HER2-amplified disease on repeat biopsy were appropriately switched to NAT with HER2-based chemotherapy. Conclusions: This phase 1 study established abemaciclib 150 mg PO BID and niraparib 100 mg PO daily as the recommended phase 2 dose for this combination. Planned correlative studies are underway. Clinical trial information: NCT04481113 . Participant characteristics. Characteristic Number of Patients (N = 8) Race White (Caucasian) 8 ECOG 0 8 Clinical Stage I 2 II 6 Histology Ductal 8 Grade 2 2 3 6 HER2 IHC 1+ 7 2+ 1
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 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,002 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| 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 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 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 ».