Serial Circulating Tumor DNA Mutational Status in Patients with KRAS-Mutant Metastatic Colorectal Cancer from the Phase 3 AIO KRK0207 Trial

Lueong, Smiths S.; Herbst, Andreas; Liffers, Sven-Thorsten; Bielefeld, Nicola; Horn, Peter A.; Tannapfel, Andrea; Reinacher-Schick, Anke; Hinke, Axel; Hegewisch-Becker, Susanna; Kolligs, Frank T. und Siveke, Jens T. (2020): Serial Circulating Tumor DNA Mutational Status in Patients with KRAS-Mutant Metastatic Colorectal Cancer from the Phase 3 AIO KRK0207 Trial. In: Clinical Chemistry, Bd. 66, Nr. 12: S. 1510-1520

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 (mut)KRAS positive patients with mCRC from the prospective multicenter phase 3 trial AIO KRK0207. Serial (mut)KRAS 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. (mut)KRAS 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. (mut)KRAS 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 (mut)KRAS 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 (mut)KRAS concentrations in mCRC has prognostic value. Post treatment (mut)KRAS concentrations 2weeks 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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0009-9147
• Sprache: Englisch