A higher ctDNA fraction decreases survival in regorafenib-treated metastatic colorectal cancer patients. Results from the regorafenib's liquid biopsy translational biomarker phase II pilot study.
circulating tumor DNA
metastatic colorectal cancer
prospective pilot study
regorafenib
sequencing
Journal
International journal of cancer
ISSN: 1097-0215
Titre abrégé: Int J Cancer
Pays: United States
ID NLM: 0042124
Informations de publication
Date de publication:
15 03 2021
15 03 2021
Historique:
received:
12
06
2020
revised:
24
08
2020
accepted:
25
08
2020
pubmed:
20
9
2020
medline:
20
7
2021
entrez:
19
9
2020
Statut:
ppublish
Résumé
The predictive effect of circulating tumor DNA (ctDNA) in colorectal cancer (CRC) treatment is still highly discussed. The primary objective of our study was to investigate a possible prognostic/predictive value of ctDNA under regorafenib treatment. This prospective multicenter translational biomarker phase II pilot study enrolled 30 metastatic CRC patients (67% men, 33% women) treated with regorafenib. ctDNA was assessed in plasma before treatment start and at defined time points during administration. Measurement of tumor fraction as well as mutation and copy number analysis of CRC driver genes were performed by next-generation sequencing approaches. Multivariate analyses for survival and treatment efficacy were adjusted to age, gender and Eastern Cooperative Oncology Group. Disease control rate was 30%. Median tumor fraction at baseline was 18.5% (0-49.9). Mutations in CRC driver genes or genes involved in angiogenesis were identified in 25 patients (83.3%). KRAS mutations were detected in 13 of 14 KRAS-positive tumors; in three patients without KRAS mutation in the respective tumors, acquired mutations as a consequence of prior anti-EGFR treatment were detected. In a subset of patients, novel occurring mutations or focal amplifications were detected. A tumor fraction of 5% and higher at baseline was significantly associated with a decreased OS (P = .022; hazard ratio 3.110 (95% confidence interval: 1.2-8.2). ctDNA is detectable in a high proportion of mCRC patients. Higher ctDNA levels are associated with survival among regorafenib treatment. Moreover, our data highlight the benefit of a combined evaluation of mutations and somatic copy number alterations in advanced cancer patients.
Identifiants
pubmed: 32949150
doi: 10.1002/ijc.33303
pmc: PMC7894541
doi:
Substances chimiques
Biomarkers, Tumor
0
Circulating Tumor DNA
0
Phenylurea Compounds
0
Pyridines
0
regorafenib
24T2A1DOYB
Banques de données
ClinicalTrials.gov
['NCT01983098']
Types de publication
Clinical Trial, Phase II
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1452-1461Informations de copyright
© 2020 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of Union for International Cancer Control.
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