Interim analysis of a single-center, single-arm, prospective phase 2 study to evaluate the efficacy and safety of benralizumab for alpelisib rash in metastatic PIK3CA-mutant, hormone receptor–positive breast cancer.
Notice bibliographique
Résumé
12100 Background: Rash associated with increased peripheral eosinophils develops in approximately 50% of metastatic breast cancer patients receiving alpelisib. Antihistamines and corticosteroids have limited benefit. Refractory rash may lead to decreased dose intensity and affect clinical outcome. Benralizumab is an anti-IL-5Rα chimeric monoclonal antibody that depletes peripheral eosinophils and has demonstrated benefit in eosinophilic asthma and hypereosinophilic syndrome. We investigate the efficacy and safety of benralizumab for the treatment of alpelisib rash. Methods: We performed a single-center, single-arm, prospective phase 2 study to evaluate the efficacy and safety of benralizumab in cancer patients who developed CTCAE grade 2/3 skin events resulting from immunotherapy or targeted therapies with absolute blood eosinophil counts of ≥300/mcl. While remaining on culprit drugs, patients were treated with benralizumab 30mg once every 4 weeks for the first 3 doses followed by once every 8 weeks for 3 additional doses (approved dosing for eosinophilic asthma). Primary endpoint was clinical response measured as reduction in CTCAE grade 2/3 skin event to grade ≤1 by week 4. Secondary endpoints were patient quality of life (QoL) measured by skindex16, safety data, need for supportive oral corticosteroids, and changes in cytokines and eosinophil biomarkers. This interim analysis focuses on patients with PIK3CA-mutant metastatic breast cancer receiving alpelisib. Results: Between September 16 th 2020 and January 1 st 2022, we enrolled 10 metastatic breast cancer patients with grade 2/3 rash attributed to alpelisib (5 pts with G3). All patients had a reduction of rash to grade ≤1 (n = 10, p < 0.0001), and a decrease in peripheral absolute eosinophils (mean 500/mcl to 0, p < 0.0001). Of these, 6 patients had been on prophylactic oral antihistamines and 2 had oral steroid coadministration. QoL significantly improved (Skindex16 mean score 58 to 16, p = 0.0001) and eosinophils in skin histology decreased per HPF (mean 6.25 to 0.25, n = 8, p = 0.2) by week 4. An increase in IL-5 > 600% and reduction IL-6 and TNF-α > 50% were reported by week 4 and 8. Grade 1/2 mucositis in 4 patients were reported as adverse events. Conclusions: Our findings suggest that benralizumab is safe and effective for the treatment of grade 2/3 rash with eosinophilia related to alpelisib in patients with breast cancer. A reduction in rash severity was evidenced in all patients, along with improved QoL. Larger controlled studies are in development to evaluate the efficacy of benralizumab for the prevention of alpelisib rash. Clinical trial information: NCT04552288.
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 | 0,005 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,003 | 0,001 |
| 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 | 0,001 |
| 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 ».