التفاصيل البيبلوغرافية
| العنوان: |
Circulating tumour DNA in patients with advanced melanoma treated with dabrafenib or dabrafenib plus trametinib: a clinical validation study |
| المؤلفون: |
Syeda, Mahrukh M, Wiggins, Jennifer M, Corless, Broderick C, Long, Georgina V, Flaherty, Keith T, Schadendorf, Dirk, Nathan, Paul D, Robert, Caroline, Ribas, Antoni, Davies, Michael A, Grob, Jean Jacques, Gasal, Eduard, Squires, Matthew, Marker, Mahtab, Garrett, James, Brase, Jan C, Polsky, David |
| المصدر: |
The Lancet Oncology, vol 22, iss 3 |
| بيانات النشر: |
eScholarship, University of California |
| سنة النشر: |
2021 |
| المجموعة: |
University of California: eScholarship |
| مصطلحات موضوعية: |
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Clinical Trials and Supportive Activities, Cancer, Clinical Research, Detection, screening and diagnosis, 4.2 Evaluation of markers and technologies, Good Health and Well Being, Aged, Antineoplastic Combined Chemotherapy Protocols, Brain Neoplasms, Circulating Tumor DNA, Double-Blind Method, Female, Follow-Up Studies, Humans, Imidazoles, Male, Melanoma, Middle Aged, Oximes, Prognosis, Pyridones, Pyrimidinones, Survival Rate, Oncology & Carcinogenesis |
| جغرافية الموضوع: |
370 - 380 |
| الوصف: |
BackgroundMelanoma lacks validated blood-based biomarkers for monitoring and predicting treatment efficacy. Cell-free circulating tumour DNA (ctDNA) is a promising biomarker; however, various detection methods have been used, and, to date, no large studies have examined the association between serial changes in ctDNA and survival after BRAF, MEK, or BRAF plus MEK inhibitor therapy. We aimed to evaluate whether baseline ctDNA concentrations and kinetics could predict survival outcomes.MethodsIn this clinical validation study, we used analytically validated droplet digital PCR assays to measure BRAFV600-mutant ctDNA in pretreatment and on-treatment plasma samples from patients aged 18 years or older enrolled in two clinical trials. COMBI-d (NCT01584648) was a double-blind, randomised phase 3 study of dabrafenib plus trametinib versus dabrafenib plus placebo in previously untreated patients with BRAFV600 mutation-positive unresectable or metastatic melanoma. Patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. COMBI-MB (NCT02039947) was an open-label, non-randomised, phase 2 study evaluating dabrafenib plus trametinib in patients with BRAFV600 mutation-positive metastatic melanoma and brain metastases. Patients in cohort A of COMBI-MB had asymptomatic brain metastases, no previous local brain-directed therapy, and an ECOG performance status of 0 or 1. Biomarker analysis was a prespecified exploratory endpoint in both trials and performed in the intention-to-treat populations in COMBI-d and COMBI-MB. We investigated the association between mutant copy number (baseline or week 4 or zero conversion status) and efficacy endpoints (progression-free survival, overall survival, and best overall response). We used Cox models, Kaplan-Meier plots, and log-rank tests to explore the association of pretreatment ctDNA concentrations with progression-free survival and overall survival. The effect of additional prognostic variables such as lactate dehydrogenase was also investigated in addition ... |
| نوع الوثيقة: |
article in journal/newspaper |
| وصف الملف: |
application/pdf |
| اللغة: |
unknown |
| العلاقة: |
qt4c11s17n; https://escholarship.org/uc/item/4c11s17nTest |
| الإتاحة: |
https://escholarship.org/uc/item/4c11s17nTest |
| حقوق: |
public |
| رقم الانضمام: |
edsbas.AC66449C |
| قاعدة البيانات: |
BASE |
