Blood‐based detection of RAS mutations to guide anti‐EGFR therapy in colorectal cancer patients: concordance of results from circulating tumor DNA and tissue‐based RAS testing

Abstract

An accurate blood‐based RAS mutation assay to determine eligibility of metastatic colorectal cancer (mCRC) patients for anti‐EGFR therapy would benefit clinical practice by better informing decisions to administer treatment independent of tissue availability. The objective of this study was to determine the level of concordance between plasma and tissue RAS mutation status in patients with mCRC to gauge whether blood‐based RAS mutation testing is a viable alternative to standard‐of‐care RAS tumor testing. RAS testing was performed on plasma samples from newly diagnosed metastatic patients, or from recurrent mCRC patients using the highly sensitive digital PCR technology, BEAMing (beads, emulsions, amplification, and magnetics), and compared with DNA sequencing data of respective FFPE (formalin‐fixed paraffin‐embedded) tumor samples. Discordant tissue RAS results were re‐examined by BEAMing, if possible. The prevalence of RAS mutations detected in plasma (51%) vs. tumor (53%) was similar, in accord with the known prevalence of RAS mutations observed in mCRC patient populations. The positive agreement between plasma and tumor RAS results was 90.4% (47/52), the negative agreement was 93.5% (43/46), and the overall agreement (concordance) was 91.8% (90/98). The high concordance of plasma and tissue results demonstrates that blood‐based RAS mutation testing is a viable alternative to tissue‐based RAS testing.

S3-Leitlinie – Kolorektales Karzinom

“…Falls die Bestimmung des RAS-oder BRAF-Mutationsstatus aus dem Gewebe nicht möglich ist, kann in Betracht gezogen werden, den Mutationsstatus aus der im Blut zirkulierenden Tumor-DNA zu ermitteln [1073]. Diese Analysen ermöglichen im Einzelfall den Nachweis einer anti-EGFR Resistenz, die sich auf dem Boden einer Expansion RAS-mutierter Klone entwickelt [1074 -1076].…”

Clinical Application of Liquid Biopsy in Targeted Therapy of Metastatic Colorectal Cancer

“…After the initial response, the disease was progressive. The patient was in good general health (ECOG 0) and refused further biopsy; therefore, a liquid biopsy as previously reported was performed [1, 2]. No RAS mutations were detected and a second-line therapy including cetuximab was initiated.…”

“…Recently, liquid biopsy, a noninvasive blood-based RAS mutation analysis of cell-free circulating tumor DNA (ctDNA), has been reported as a suitable method for mutational analysis in patients with mCRC [1, 2]. In contrast to tissue based RAS status determination, liquid biopsy is able to address tumor heterogeneity and treatment-related dynamic changes of molecular profiles [3–6].…”

“…In contrast to tissue based RAS status determination, liquid biopsy is able to address tumor heterogeneity and treatment-related dynamic changes of molecular profiles [3–6]. The possibility to monitor the RAS status by liquid biopsy [2–6] during disease progression directed the focus onto the dynamic of mutational changes during therapy. The benefit of therapy adaptation for patients based on the monitored RAS status is not addressed so far by studies concerning mCRC.…”

Monitoring the effect of first-line treatment in RAS/RAF mutated metastatic colorectal cancer by serial analysis of tumor specific DNA in plasma.

“…In the clinic the mutation analysis thus serves as a tool for selection of targeted treatment. New data show that ctDNA may replace tumor tissue analysis [5][6][7][8], and serial analysis may provide information as to the relation of ctDNA with treatment effect and progression [9]. There are few studies in solid tumors dealing with this issue.…”