Abstract PD1-10: Randomized phase II study comparing two different schedules of palbociclib plus second line endocrine therapy in women with estrogen receptor positive, HER2 negative advanced/metastatic breast cancer: CCTG MA38 (NCT02630693)
Notice bibliographique
Résumé
Abstract Background: Palbociclib is approved for treatment of ER+, HER2- ABC at a standard dose of 125 mg po daily 3 weeks on/1 week off (STD). We evaluated the efficacy, safety, quality of life (QOL) and compliance of a 100 mg continuous daily dose (CDD) of palbociclib based on modeling data that suggested efficacy and tolerability. Methods: Canadian Cancer Trials Group (CCTG) led a randomized phase II trial (CCTG MA38) to estimate the efficacy of palbociclib 100 mg po on CDD schedule (Arm 1) relative to 125 mg po STD schedule (Arm 2) with physician choice endocrine therapy. Eligible patients had ER+, HER2- ABC, post progression on first line metastatic endocrine therapy or progressed while on/within 12 months of completion of adjuvant endocrine therapy. One line of palliative chemotherapy in ABC was allowed. Stratification factors were: visceral metastases, duration of prior endocrine therapy and planned endocrine therapy. Primary Outcome measure was investigator reported PFS; secondary outcome measures included: RR, OS, safety (CTCAE V4.0), and QOL (EORTC QLQ-C30). The sample size was 180 to enable estimation of the HR between arms with the upper bound of the 90% CI 1.36 times the estimated HR and the lower bound is 0.74 times the estimated HR. Results: 180 patients were enrolled across Canada from Dec 2015 to Feb 2017. The database was locked April 16 2018 after prespecified PFS events reached at a median follow-up of 19 months for all patients. For the whole population: median age was 60.5 years (21% ≥ 70 years); ECOG 0/1 95%; postmenopausal 91%; visceral metastases 67%. Planned endocrine therapy: aromatase inhibitor 33%, fulvestrant 57%, tamoxifen 10%. Efficacy analyses CDD vs STD: PFS stratified univariate HR 0.93 (90% CI 0.66-1.30); multivariate Cox model analysis (covariates ECOG PS, age, histology, grade): HR 0.92 (90% CI 0.67-1.25). Median PFS CDD: 9.33 months (90% CI 6.93-13.90) and STD: 11.30 months (90% CI 8.08- 13.83) Secondary analyses CDD vs STD: OS stratified univariate HR: 1.07 (90% CI 0.67-1.69); multivariate HR 1.14 (90%CI 0.75-1.75); median OS for CDD: 20.73 months (90% CI 19.29-23.30) and 21.39 months (90% CI 19.65 to 26.68) for STD. RR and median duration of response: 11.1% vs 12.4% (p=0.84) and 126 vs 169 days (p=0.86), respectively. Palbociclib drug exposure CDD vs STD: median daily dose (mg) 87 vs 125; median dose intensity (mg/week) 571.2 vs 613.5; ≥ 90% planned dose intensity, 41% vs 54%. Dose modification (withhold and/or reduction) rate CDD vs STD for neutropenia was 70% vs 40%. Grade 3/4 neutropenia 69% vs 53%; febrile neutropenia 3% each arm. Non-hematological toxicity profiles were comparable for both arms. No significant differences were seen in QOL domains. Conclusion: Palbociclib is active and tolerable when administered on either a 100 mg CDD or a 125 mg STD schedule. CDD schedule had higher rates of grade 3/4 neutropenia and dose modifications. Post approval evaluation of alternate dosing schedules for targeted therapies provides useful information regarding drug activity, toxicity and adherence. Citation Format: Parulekar WR, Joy AA, Gelmon K, Mates M, Desbiens C, Clemons M, Taylor S, Lemieux J, Bartlett J, Whelan T, Ayoub J-P, Cescon D, Bordeleau L, Rahim Y, Winch C, Chen BE. Randomized phase II study comparing two different schedules of palbociclib plus second line endocrine therapy in women with estrogen receptor positive, HER2 negative advanced/metastatic breast cancer: CCTG MA38 (NCT02630693) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr PD1-10.
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) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,003 | 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 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,008 | 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 ».