Abstract P1-18-05: Early changes in circulating tumor DNA and its effect on clinical outcomes in patients with advanced breast cancer receiving the CDK4/6 inhibitor palbociclib: Genotyping results from POLARIS
Notice bibliographique
Résumé
Abstract Background: POLARIS is a prospective, real-world study of palbociclib in patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2–) advanced breast cancer (ABC) in the United States and Canada. These analyses evaluated the difference in tumor mutation profiles of patients receiving palbociclib in the first line versus second line or greater and examined the applicability of circulating tumor DNA (ctDNA) monitoring in a real-world setting. Methods: The clinical database cut-off date was March 16, 2021. Patients in the biomarker analysis group provided consent for serial blood sample collections, received ≥1 dose of initial palbociclib combination treatment, and had ≥1 ctDNA measurement available. The Guardant360 platform with somatic single-nucleotide variants in complete or critical exons of 73 genes was used. The association between early changes in ctDNA mutation allele fractions at Cycle 2 Day 1 (C2D1) and disease progression at Week 24 was evaluated using univariate and multivariable logistic regression analysis adjusting for line of therapy. Results: Among patients with HR+/HER2– ABC (N=347), 93.9% (n=326) had ctDNA measured at baseline, of which 85.9% (n=280) had ≥1 ctDNA alteration detected; 66.6% of patients received palbociclib treatment in the first line and 33.4% as second line or greater ABC setting. The frequencies of gene mutations at baseline were generally higher in patients receiving palbociclib as a second-line or greater therapy compared to those who received it as first-line therapy, particularly for ESR1 mutations (30% vs 15%) and FGFR1 mutations (13% vs 9%). With a median (range) follow-up duration of 18.5 (0.1-46.3) months, patients with total ctDNA increase at C2D1 (log ratio change >0) were 3.74 times more likely to have disease progression at Week 24 (odds ratio, 3.74 [95% CI, 1.71-8.17]; P=0.001) compared with those without change or with a decrease in ctDNA at C2D1 (log ratio change ≤0). The observed significant association remained after adjusting for line of therapy in the multivariable regression analysis (odds ratio, 2.62 [95% CI, 1.14-6.04]; P=0.023). Conclusions: Among patients with HR+/HER2- ABC receiving palbociclib, early changes in ctDNA mutations were significantly associated with disease progression. Further studies are needed to confirm these findings and to evaluate the clinical utility of ctDNA-guided “adaptive” early therapeutic interventions to improve outcomes in patients with metastatic breast cancer. Pfizer; NCT03280303 Citation Format: Debu Tripathy, Zhe Zhang, Joanne L. Blum, Meghan S. Karuturi, Steven L. McCune, Bijoy Telivala, Shailendra Lakhanpal, Kamal Patel, Richard C. Frank, Kit Lu, Chetan Deshpande, Yao Wang, Yuan Liu, Aditya Bardia. Early changes in circulating tumor DNA and its effect on clinical outcomes in patients with advanced breast cancer receiving the CDK4/6 inhibitor palbociclib: Genotyping results from POLARIS [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-18-05.
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 | 0,002 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,002 |
| 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 ».