Abstract 461P
Background
Tumour heterogeneity represents a possible source of error in detecting predictive genetic alterations in tumour tissue and can be overcome by testing for alterations in circulating tumour DNA (ctDNA) using liquid biopsy.
Methods
108 patients with a diagnosis of metastatic colorectal cancer (mCRC) were assessed for the presence of RAS/BRAF mutations in ctDNA in our Oncology Unit. Patients were divided in two cohorts: 53 patients assessed before treatment initiation (basal cohort) and 55 patients assessed after anti-EGFR treatment (post-EGFR cohort). KRAS, NRAS and BRAF mutation analysis in plasma was performed using a fully automated real time PCR-based platform (Idylla™ Biocartis). We evaluated the performance of this technique compared to tissue analysis and correlated the results to patients’ clinical features.
Results
The overall agreement between tissue analysis and liquid biopsy in the basal cohort was 81.13%, with a higher concordance in patients with liver metastases (88.57%). In patients with liver metastases, sensitivity, specificity, and positive predictive value (PPV) of liquid biopsy were 84.21%, 93.75%, and 94.12%, respectively. Circulating mutational fraction (CMF) for KRAS was significantly higher in patients with liver metastases. In one case of metachronous metastases, the detection of a RAS mutation in plasma but not on tissue analysis predicted the lack of response to anti-EGFR treatment. In the post-EGFR cohort, 13/55 patients presented detectable mutations in KRAS (9 cases), NRAS (3 cases) or BRAF (1 case) in plasma. Among the KRAS mutants, the prevalence of non-exon2 mutations was higher in the post-EGFR cohort (44%) compared to the basal cohort (21%). CMF values for KRAS increased significantly (P: 0.0313) in patients receiving a rechallenge anti-EGFR treatment.
Conclusions
Real time PCR-based testing of RAS/BRAF mutations in plasma is feasible and reliable in mCRC patients in a clinical setting. Liver involvement increases the reliability of the technique. Plasma detection of RAS mutations has a strong clinical value in case of metachronous metastatic disease. Liquid biopsy is useful to monitor the onset and fluctuations of RAS mutations in patients receiving anti-EGFR therapy.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Università della Campania \"Luigi Vanvitelli\".
Disclosure
P.P. Vitiello: Advisory/Consultancy: Biocartis. T. Troiani: Advisory/Consultancy: Amgen; Advisory/Consultancy: Bayer; Advisory/Consultancy: Merck; Advisory/Consultancy: Novartis; Advisory/Consultancy: Roche; Advisory/Consultancy: Sanofi. F. Ciardiello: Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy, Research grant/Funding (institution): Roche; Advisory/Consultancy, Research grant/Funding (institution): Amgen; Advisory/Consultancy, Research grant/Funding (institution): Bayer; Advisory/Consultancy: Servier; Advisory/Consultancy: Symphogen; Advisory/Consultancy: Pfizer; Research grant/Funding (institution): Ipsen. E. Martinelli: Advisory/Consultancy: Amgen; Advisory/Consultancy: Bayer; Advisory/Consultancy: Merck; Advisory/Consultancy: Roche; Advisory/Consultancy: Servier; Advisory/Consultancy: Sanofi. All other authors have declared no conflicts of interest.