Back to Search
Start Over
Serial Circulating Tumor DNA Mutational Status in Patients with KRAS-Mutant Metastatic Colorectal Cancer from the Phase 3 AIO KRK0207 Trial
- Publication Year :
- 2020
-
Abstract
- Background We assessed the usefulness of circulating tumor DNA (ctDNA) pre- or post-treatment initiation for outcome prediction and treatment monitoring in metastatic colorectal cancer (mCRC). Methods Droplet digital PCR was used to measure absolute mutant V-Ki-ras2 Kirsten rat sarcoma viral oncogene ((mut)KRAS) ctDNA concentrations in 214 healthy controls (plasma and sera) and in 151 tissue-based mutKRAS positive patients with mCRC from the prospective multicenter phase 3 trial AIO KRK0207. Serial mutKRAS ctDNA was analyzed prior to and 2–3 weeks after first-line chemotherapy initiation with fluoropyrimidine, oxaliplatin, and bevacizumab in patients with mCRC and correlated with clinical parameters. Results mut KRAS ctDNA was detected in 74.8% (113/151) of patients at baseline and in 59.6% (90/151) at follow-up. mutKRAS ctDNA at baseline and follow-up was associated with poor overall survival (OS) (hazard ratio [HR] =1.88, 95% confidence interval [CI] 1.20–2.95; HR = 2.15, 95% CI 1.47–3.15) and progression-free survival (PFS) (HR = 2.53, 95% CI 1.44–4.46; HR = 1.90, 95% CI 1.23–2.95), respectively. mutKRAS ctDNA clearance at follow-up conferred better disease control (P = 0.0075), better OS (log-rank P = 0.0018), and PFS (log-rank P = 0.0018). Measurable positive mutKRAS ctDNA at follow-up was the strongest and most significant independent prognostic factor on OS in multivariable analysis (HR = 2.31, 95% CI 1.40–3.25). Conclusions Serial analysis of circulating mutKRAS concentrations in mCRC has prognostic value. Post treatment mutKRAS concentrations 2 weeks after treatment initiation were associated with therapeutic response in multivariable analysis and may be an early response predictor in patients receiving first-line combination chemotherapy. Clinicaltrialsgov Identifier NCT00973609.
- Subjects :
- 0301 basic medicine
Oncology
medicine.medical_specialty
Bevacizumab
Colorectal cancer
medicine.medical_treatment
Clinical Biochemistry
Medizin
medicine.disease_cause
Circulating Tumor DNA
Proto-Oncogene Proteins p21(ras)
03 medical and health sciences
0302 clinical medicine
Internal medicine
Biomarkers, Tumor
medicine
Humans
Prospective Studies
Liquid biopsy
Chemotherapy
business.industry
Biochemistry (medical)
Hazard ratio
Combination chemotherapy
Prognosis
medicine.disease
Oxaliplatin
030104 developmental biology
030220 oncology & carcinogenesis
Colonic Neoplasms
Mutation
KRAS
Colorectal Neoplasms
business
medicine.drug
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....514fea7129f67cf510b755fce60c976b