Abstract P1-19-16: Long-term pooled safety analysis of palbociclib in combination with endocrine therapy for hormone receptor-positive/human epidermal growth factor receptor 2–negative advanced breast cancer: An updated analysis
Notice bibliographique
Résumé
Abstract Background Palbociclib (PAL) in combination with endocrine therapy (ET) was shown to be tolerable in a previous pooled analysis of the 3 PALOMA clinical trials. This new pooled, post hoc analysis examines the safety profile of PAL + ET using data from more recent data cutoff dates with longer drug exposure. Methods Data were pooled from 3 randomized phase 2 and 3 studies of patients with hormone receptor-positive/human epidermal growth factor receptor 2–negative advanced breast cancer (HR+/HER2- ABC). Postmenopausal first-line patients were randomized to receive letrozole (2.5 mg/d, continuously) +/- PAL (125 mg/d, 3/1 schedule) in PALOMA-1 or letrozole (2.5 mg/d, continuously) + PAL (125 mg/d, 3/1 schedule)/placebo in PALOMA-2. In PALOMA-3, pre/peri- and postmenopausal patients with prior endocrine resistance received intramuscular fulvestrant (500 mg every 14 days for the first 3 injections, then every 28 days) + PAL (125 mg/d, 3/1 schedule)/placebo. The cumulative rates of adverse events (AEs) were assessed over time. Results Updated data cutoff dates used for this analysis were December 21, 2017 (PALOMA-1), May 31, 2017 (PALOMA-2), and April 13, 2018 (PALOMA-3). The total number of person-years of exposure was 1950 (1422 PAL + ET, 528 ET). In the ET arm (n=471), 20.2% of patients were treated for ≥24 months and 10.2% were treated for ≥36 months. In the PAL + ET arm (n=872), 36% of patients were treated for ≥24 months and 22.4% for ≥36 months. The majority of patients treated for ≥24 and ≥36 months in the PAL + ET arm were from PALOMA-2. As expected, neutropenia and infections (any grade) were more frequent with PAL + ET (82.1% and 59.2%, respectively) than in the ET arm (5.1% and 39.5%). Febrile neutropenia was reported in 1.4% of patients in the PAL + ET arm. The incidence of hematologic AEs in the PAL + ET arm peaked during the first year of treatment and then plateaued over the subsequent 5 years. Serious AEs were reported in 22.8% of patients in the PAL + ET arm and 15.5% in the ET arm. Selected cumulative grade 3/4 event rates through 5 years were neutropenia (68.3% in PAL + ET; 0.8% in ET), leukopenia (29.9%; 0.2%), infections (6.4%; 2.8%), anemia (5.3%; 2.1%), fatigue (2.9%; 1.3%), alanine aminotransferase increased (2.2%; 0.2%), aspartate aminotransferase increased (2.9%; 1.3%), diarrhea (1%; 1.1%), nausea (0.6%; 1.3%), vomiting (0.7%; 1.1%), and QTc prolongation (0.3%; 0.2%). After adjusting for treatment exposure, incidence rates of venous thromboembolism and pulmonary embolism were 0.0225 (PAL + ET) and 0.0246 (ET) per person-year and 0.0127 (PAL + ET) and 0.0132 (ET) per person-year, respectively. Conclusion This 5-year, long-term safety analysis of PAL + ET showed a consistent profile with no new safety signals, and no cumulative/delayed toxicities. PAL + ET remains a safe and manageable treatment for patients with HR+/HER2- ABC. Pfizer (NCT00721409, NCT01740427, NCT01942135) Citation Format: Richard S Finn, Hope S Rugo, Karen Gelmon, Massimo Cristofanilli, Marco Colleoni, Sherene Loi, Patrick Schnell, Dongrui R Lu, Kathy P Theall, Ave Mori, Eric Gauthier, Eustratios Bananis, Nicholas C Turner, Véronique Diéras. Long-term pooled safety analysis of palbociclib in combination with endocrine therapy for hormone receptor-positive/human epidermal growth factor receptor 2–negative advanced breast cancer: An updated analysis [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-19-16.
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 | 0,021 | 0,019 |
| Méta-épidémiologie (sens strict) | 0,002 | 0,001 |
| Méta-épidémiologie (sens large) | 0,005 | 0,016 |
| Bibliométrie | 0,002 | 0,003 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,003 | 0,001 |
| Science ouverte | 0,001 | 0,001 |
| Intégrité de la recherche | 0,001 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,004 | 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 ».