Extended RAS Mutational Status Analysis in Circulating Tumor DNA from Patients with Advanced Colorectal Cancer in Daily Clinical Practice. The Franco-British Institute Experience and Recommendations
Journal Title: Biomedical Journal of Scientific & Technical Research (BJSTR) - Year 2018, Vol 6, Issue 5
Abstract
Background : The development of liquid biopsies could help clinicians to shorten treatment decision and allow longitudinal molecular monitoring. We report here our experience of using the Biocartis IdyllaTM test for patients with advanced colorectal cancer in daily clinical practice. Patients and Methods: This program prospectively enrolled patients with advanced colorectalcancer at the Department of Medical Oncology of the Franco-British Institute, Levallois-Perret,France.Theprimary objective was to evaluate the feasibilty of the IdyllaTM testing in daily clinical practice. Results: From November 17, 2017 to June 12,2018, 50 patients were tested. The median time to circulating tumor (ct) extended mutational status was 4.8 hours (95% CI:4.7-5.1). Among 37 (74.0%) patients with paired plasma and tumor samples available, the overall agreement rate was 73.0%. In patients with previously untreated metastatic liver disease (n=9;18%), the overall agreement rate between paired plasma and tumor samples was 100.0%, and the weighted K coefficient was 1.00 (95% CI: 1.00-1.00). Conclusion : Extended RAS mutational status analysis in circulating tumor DNA from patients with advanced colorectal cancer is feasible and greatly helpful for daily clinical practice. We recommend restricting ctDNA testing with IdyllaTM to patients with previously untreated liver metastatic disease.Systemic therapy is the standard care for patients with unresectable metastatic colorectal cancer (CRC). Cetuximab and panitumumab are IgG monoclonal antibodies (MoAb), which competitively inhibit the binding of epidermal growth factor (EGF) and other ligands to EGF receptor (EGFR) and downregulate EGFR, resulting in inhibition of cell survival, growth, proliferation, and transformation. Tumor molecular testing for Kirsten rat sarcoma viral oncogene homolog (KRAS) and Neuroblastoma RAS viral oncogene homolog (NRAS) tumor genes is mandatory in order to select MCRC patients who may benefit from anti-EGFR MoAb therapy [1]. In 2014, the mean time to obtain the RAS genotyping test report in France was 25 days, and for 25% of the patients it was more than one month [2]. The murine sarcoma viral (v-Raf) oncogene homolog B (BRAF) is a human gene that encodes BRAF, a protein involved in sending signals inside cells, which are involved in directing cell growth. The BRAF V600E mutation is found in10% of patients with colorectal adenocarcinoma [3] and BRAF mutant tumors are more frequently right-sided, mucinouswith peritoneal spreadand microsatellite instability [4].The extracellular domain (ECD) of EGFR p.S492 mutation has been described as an acquired resistance to cetuximab [5]. The development of liquid biopsies could help clinicians to shorten treatment decision and allow longitudinal molecular monitoring. The concordance between plasma and tumor RAS mutational status ranges from 84% to 100% depending on different techniques (duplex dPCR, allele specific quantitative PCR, BEAMing [OncoBEAM] or NGS BPER) [6-13]. We report here our experience of using the Biocartis IdyllaTM test for daily clinical practice in order to improve care in patients with advanced CRC.
Authors and Affiliations
Laurence Heuls, Nathalie Perez Staub, Ida Iurisci, Perrine Goyer, Arnaud Saget, Hubert Richa, Hélène Marijon, Linda Dainese, Annette K Larsen, Aimery De Gramont, Benoist Chibaudel
Keywords
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- EP ID EP588493
- DOI 10.26717/BJSTR.2018.06.001409
- Views 177
- Downloads 0
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