For identifying patients with metastatic colorectal cancer who might benefit from therapy with drugs targeted against the epidermal growth factor receptor (EGFR), analysis of plasma for circulating tumor DNA – aka “liquid biopsy” – is about as capable as and considerably faster than tissue analysis of RAS mutational status, investigators contend.
Among 412 chemotherapy-naive patients with metastatic colorectal cancer (mCRC) for whom both plasma and tissue samples were available, the kappa coefficient (a measure of acceptable concordance) between ctDNA RAS mutation detection and tissue-based analysis was 0.71, just over the minimum 0.7, and the accuracy of the liquid biopsy sampling was 85.2%, reported Pierre Laurent-Puig, MD, PhD, of Sorbonne University in Paris, and his colleagues.
“[E]ven if our results are limited to the techniques used with their analytic sensitivity, we show here for the first time in a prospective study an excellent concordance between plasma and tumor RAS mutation status in metastatic colorectal cancer patients, especially those with liver metastases. These results validate the routine use of plasma RAS analysis in patients with colorectal cancer and liver metastases,” they wrote. The report was published in Annals of Oncology.
The investigators found that ctDNA was more likely to yield inconclusive results in patients without liver metastases. In patients with liver metastases, the accuracy of the liquid biopsy using next-generation sequencing (NGS) alone to detect RAS mutations was 93.5%, and when detection of methylated biomarkers was added in, the accuracy was 97%.
In the AGEO RASANC prospective multicenter study, the investigators prospectively collected plasma samples from patients with mCRC and sent them to a central lab for analysis by NGS with the colon/lung cancer V2 Ampliseq panel and with digital polymerase chain reaction dPCR for genes associated with DNA methylation (WIF1 and NPY).
Matched tissue samples from the same patients were analyzed locally according to routine practice.
As noted before, the kappa coefficient was 0.71, indicating that agreement between the tests was at least 70% better than by chance alone.