Abstract P4-22-03: Palbociclib in combination with endocrine therapy in treatment-naive and previously treated elderly women with HR+, HER2– advanced breast cancer: a pooled analysis from randomized phase 2 and 3 studies
Notice bibliographique
Résumé
Abstract Background: At least 40% of breast cancers are diagnosed in women ≥65 y old and most are hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-). Palbociclib (PAL) is an oral, small-molecule inhibitor of cyclin-dependent kinases 4 and 6. Randomized studies of PAL combined with endocrine therapy (ET) demonstrated significantly improved progression-free survival (PFS) in patients (pts) with treatment-naive and previously treated advanced breast cancer (ABC). Methods: We evaluated the efficacy of PAL+ET vs ET alone in pts aged ≥65-74 and ≥75 y across multiple pivotal randomized phase 2 and 3 studies. Safety and pharmacokinetics (PK) data (blood samples collected from pts in phase 1/2 [PALOMA-1] and phase 1 studies [NCT00141297 and NCT00420056]) for PAL+ET were pooled and compared across age groups. Pts who had not received treatment for ABC were randomized to receive PAL+letrozole (LET) or LET alone/with placebo (PBO; PALOMA-1, open-label/PALOMA-2, double-blind). Pts who had progressed on prior ET were randomized to receive PAL+fulvestrant (FUL) or PBO+FUL (PALOMA-3, double-blind). The primary endpoint for these studies was investigator-assessed PFS. Safety assessments and blood counts occurred at baseline and every 2 weeks for the first 2 cycles and on day 1 of subsequent cycles. Results: Among 872 pts treated with PAL+ET, 221 (25%) were aged ≥65-74 y and 83 (10%) were ≥75 y (PAL+LET: n=528, 162 and 56, respectively; PAL+FUL: n=347, 59 and 27). Median (range) treatment durations were 440 (1-1615) d, 502 (1-1615) d, and 459 (21-1404) d, respectively. Improvement in efficacy endpoints was seen with PAL+ET vs ET across all age groups (Table 1). Incidence of adverse events (AEs), serious AEs and discontinuations due to AEs were similar in the overall population (99%, 19%, 3%) and in pts aged ≥65-74 (99%, 25%, 5%) and ≥75 y (100%, 30%, 6%). Incidence of all grades and grade 3/4 neutropenia were also similar across age groups (overall: 67% and 54%; ≥65-74 y: 64% and 51%; ≥75 y: 77% and 60%). PK analysis showed no clinically relevant differences between arithmetic means, medians, and geometric means of the apparent oral clearance across age groups. Conclusions: PAL in combination with ET is an effective and well-tolerated treatment option for elderly pts with HR+/HER2- endocrine-sensitive and -resistant ABC. A dose adjustment based on age is not required. Sponsor: Pfizer Table 1. PFS in pts ?65-74 and ?75 y (ITT populations)OverallAged ≥65-74 yAged ≥75 yPALOMA-1/PALOMA-2PAL+LET vs528 vs 303162 vs 9456 vs 26LET/LET+PBO,* nHR (95% CI);0.53 (0.44-0.64);0.66 (0.45-0.97);0.31 (0.16-0.61);1-sided P value<0.00010.01620.0002Median PFS (95% CI), mo24.4 (22.0-26.2) vs27.5 (24.2-NR) vsNR (19.2-NR) vs13.6 (11.1-16.4)21.8 (16.3-31.3)10.9 (4.9-24.9)PALOMA-3PAL+FUL vs347 vs 17459 vs 3727 vs 6FUL+PBO, nHR (95% CI);0.46 (0.36-0.59);0.25 (0.14-0.45);0.87 (0.27-2.79);1-sided P value<0.0001<0.00010.4074Median PFS (95% CI), mo9.5 (9.2-11.0) vs16.1 (12.0-NR) vs13.6 (7.5-NR) vs4.6 (3.5-5.6)3.7 (1.9-5.3)7.4 (1.9-NR)HR=hazard ratio; ITT=intent to treat; NR=not reached. *Does not include 5 pts from phase 1 of PALOMA-1. Citation Format: Rugo HS, Turner NC, Finn RS, Joy AA, Verma S, Harbeck N, Moulder S, Masuda N, Im Y-H, Zhang K, Kim S, Sun W, Schnell P, Huang-Bartlett C, Slamon D. Palbociclib in combination with endocrine therapy in treatment-naive and previously treated elderly women with HR+, HER2– advanced breast cancer: a pooled analysis from randomized phase 2 and 3 studies [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-22-03.
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 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,002 | 0,000 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| 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 ».