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 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 | 0,010 | 0,007 |
| Méta-épidémiologie (sens strict) | 0,002 | 0,001 |
| Méta-épidémiologie (sens large) | 0,005 | 0,010 |
| Bibliométrie | 0,001 | 0,002 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,002 | 0,001 |
| Science ouverte | 0,001 | 0,001 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 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 ».