Accurate detection of RAS mutations in metastatic colorectal cancer (mCRC) patients is of high clinical importance for therapy selection as RAS detection methods lacking sensitivity may lead to poor patient outcomes. Liquid biopsy has emerged as a viable alternative to individualize the management and treatment of mCRC patients. The objective of this study was to provide a head-to-head comparison of the sensitivity of two tests for KRAS mutation detection in plasma from mCRC patients: dPCR-based OncoBEAM and qPCR Idylla.
Plasma samples from mCRC patients determined to be KRAS-positive using OncoBEAM were re-tested using Idylla. 116 samples with mutant allelic fractions (MAF) below 5% were selected for analysis. The positive percent agreement (PPA) of KRAS mutation results was compared for replicate samples analyzed by OncoBEAM and Idylla.
Idylla detected KRAS mutations in 81 out of 116 (69.8%, p < 0.0001) OncoBEAM KRAS-positive plasma samples. Categorization of results based on MAF% revealed distinct differences in sensitivity between the two technologies.Table: 550P
|MAF% Range||PPA Idylla vs OncoBEAM|
|1-5%||89.1% (33/37) (p = 0.1336)|
|0.1-1%||65.1% (41/63) (p < 0.0001)|
|0.02%-0.1%||43.8% (7/16) (p = 0.0077)|
Significant differences have been observed in patients with liver and other metastases, except lung, 41/51 (80.4%, p = 0.0044) and patients with lung and other metastases, except liver, 16/24 (66.7%, p = 0.0133).
OncoBEAM demonstrated significantly greater sensitivity for plasma detection of RAS mutations than Idylla. Moreover, these data identify a “gray zone” below 1% MAF where Idylla fails to identify RAS-positivity in patient plasma samples. These findings show that liquid biopsy assays with diminished sensitivity may lack the dynamic range to provide accurate and timely RAS mutational status information to properly guide highly individualized anti-EGFR therapy and chemotherapy treatment decisions that may benefit patient outcomes.
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A. Vivancos: Consultant: Sysmex Inostics. All other authors have declared no conflicts of interest.