First Results from FACT – An Open-Label, Randomized Phase III Study Investigating Loading Dose of Fulvestrant Combined with Anastrozole Versus Anastrozole at First Relapse in Hormone Receptor Positive Breast Cancer.
Notice bibliographique
Résumé
Abstract Background:Although aromatase inhibitors, including anastrozole (A) have been shown to be effective for treatment of hormone-dependent postmenopausal breast cancer, many patients with advanced disease will develop resistance. Fulvestrant (F) down regulates estrogen receptors in human breast cancer and has similar single agent activity as A and tamoxifen. Fulvestrant demonstrates a dose-response effect and the present standard dosing strategy takes 3-6 months to reach pharmokinetically sufficient drug levels. Combining A with F might counteract resistance by increasing estrogen blockade through different, yet synergistic modes of action A lowering estrogen levels and F antagonizing and down-regulating the estrogen receptor. Here, the combination of F+A vs A was investigated at first relapse in hormone receptor positive breast cancer in the phase III FACT study, by using a loading dose (LD) schedule followed by monthly injections of F, with the aim to overcome some endocrine resistance mechanisms by maximal estrogen blockade and to use F more optimally.Methods:Postmenopausal women, or premenopausal women receiving a GnRH agonist, with ER+ and/or PgR+ disease at first relapse following primary treatment of localized disease, were randomized to F LD (500 mg i.m. day 0, 250 mg day 14 and 28, then 250mg monthly thereafter) + 1 mg A daily, or 1 mg A daily alone at first relapse. The primary endpoint was time to progression (TTP). Secondary endpoints included objective response rate (ORR), clinical benefit rate (ORR + stable disease ≥24 weeks) (CBR), overall survival (OS) and tolerability. With 512 patients, approximately 380 events were required to detect a 3 month increase in TTP (5% two-sided significance level with 80% power).Results:514 patients, 256 in A alone group and 258 in F+A group, were randomized and approximately 2/3 of the full analysis set were either endocrine-naïve patients or patients with recurrence ≥12 month's gap following completion of adjuvant endocrine therapy. The study is mature while disease progression was demonstrated in 78.1% in the A alone group and 77.5% in the F+A combination group (HR 0.99; CI 95% 0.81-1.20, p-value 0.91). Investigator assessed ORR using the RECIST criteria on patients with measurable disease was 33.6% for the A alone group (38/113), and 31.8% for the F+A combination group (41/129) (odds ratio (OR) 0.92; 95% CI 0.54-1.58), respectively. The CBR rates were 55.1% for A and 55.0% for the F+A combination, respectively. F+A is a well-tolerated combination, but with an increased incidence of hot flushes over A alone. A total of 156 patients (61.4%) in the A alone group and 155 (60.5%) in the F+A combination group reported AEs. AEs for both groups were predominantly mild or moderate in intensity, whereas AEs CTC 3 or higher occurred in 16.9% vs 16.4%. 11 deaths due to side effects were recorded in the F+A arm and 5 in the A alone arm. In the investigator&s opinion, none of these AEs were causally related to study treatment.Discussion:Despite convincing preclinical data supporting the combined therapy strategy of fulvestrant plus an aromatase inhibitor, the present prospective, randomized study did not demonstrate any advantage by adding fulvestrant to anastrozole. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 23.
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 | 0,002 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,002 | 0,001 |
| Méta-épidémiologie (sens large) | 0,003 | 0,002 |
| Bibliométrie | 0,001 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,002 | 0,003 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,005 | 0,001 |
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 ».