Non-Infectious Pneumonitis (NIP) in Breast Cancer (BC) Patients (Pts) Treated with Everolimus (Afinitor™) Containing Therapy: Analysis of Five Studies.
Notice bibliographique
Résumé
Abstract Background: Everolimus (E), an oral mTOR inhibitor, has been and is currently being evaluated in combination with antitumor therapies for the treatment of BC. NIP is an infrequent but serious adverse event (AE) observed with mTOR inhibitors; NIP pathogenesis has not been clearly established. This analysis provides a descriptive summary of this AE in the BC trials reported with E to date. Materials and Methods: Overall 269 pts were treated with E-containing therapy in 5 BC studies (Table). In most pts, NIP was diagnosed and monitored by CT imaging and pulmonary function tests (spirometry, DLCO, room air O2 saturation at rest). Management guidelines based on worst grade (G) were implemented since phase 1 protocols and include: G1 no specific therapy required and continue treatment at full dose; G2/G3 short course of corticosteroids and hold and/or reduce E until improvement to ≤G1; G4 discontinuation of the treatment. Results: Few cases of NIP (2.9%) were reported in a phase 2 study of neoadjuvant E combined with letrozole for 4-months, in which chest assessments were not routinely requested (Baselga, J Clin Oncol, 2009). All 3 cases of NIP that were reported as severe AEs were resolved within 15 days of E discontinuation. In metastatic BC pretreated pts, E has been investigated in a NCI-C CTG phase 2 study (Ellard, J Clin Oncol, in press). In this study an overall NIP rate of 41% was reported, and was the reason for therapy discontinuation in 5 pts (10%). Most cases (35%) were G1 or G2, with subtle radiological changes (patchy ground-glass changes over the lung parenchyma) in the absence of clinical symptoms, or with a rapid resolution of symptoms and findings after dose reduction/treatment suspension, or corticosteroid use. In all cases, resolution of NIP occurred. In HER2+ heavily pretreated metastatic BC pts, the combination of E, trastuzumab, and paclitaxel or vinorelbine, has been investigated in 2 phase 1 studies (n=64) (O'Regan, SABCS 2008; Fasolo, SABCS 2008). Per protocols, these patients were regularly assessed with chest CT scans or X-rays every 8-9 weeks and received corticosteroids, anti-histamines, and H-2 antagonists as premedication. NIP at the time of the analysis was observed in 1 case: the pt developed a G3 event after 6 cycles and permanently discontinued treatment. After prednisolone treatment, the pt recovered within 13 days. Conclusion: NIP is an infrequent and manageable event in pts with BC treated with E alone or in combination regimens. Routine radiological screening of the chest can ensure early detection and appropriate management of this AE. Non-infectious pneumonitis n (%)AuthorStudy PhaseBC SettingN*RegimenG1/G2G3Baselga, 2009Ph 2, randomizedEstrogen receptor+neoadjuvant138E 10mg/d + L for 16 wks1 (0.7%)3 (2.2%)Ellard, 2009Ph 2, randomizedMetastatic49E 10mg/d or 70mg/wk17 (35%)3 (6%)Awada, 2008Ph 1bMetastatic18E 5-10mg/d + L00O'Regan, SABCS 2008Ph 1bHER2+ metastatic27E 5-10 mg/d or 30mg/wk + H + P01 (3.7%)Fasolo, SABCS 2008Ph 1bHER2+ metastatic37E 5mg/d or 20-30mg/wk + H + V00H, trastuzumab 2 mg/kg weekly; L, letrozole 2.5mg daily; P, paclitaxel 80 mg/m² Day 1, 8, 15 q4w; V, vinorelbine 25 mg/m² Day 1, 8 q3w. *N = patients treated with E-containing therapy. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1115.
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 | 0,009 | 0,007 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,005 |
| Bibliométrie | 0,003 | 0,003 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,000 | 0,001 |
| Intégrité de la recherche | 0,001 | 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 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 ».