In Depth: Performance Comparison of OncoBEAM™ RAS CRC and Idylla™ ctKRAS Liquid Biopsy Testing for KRAS Mutation Detection Presented at ASCO GI 2018

HAMBURG, Germany, January 22, 2018 /PRNewswire/ --

Sysmex Inostics, a global leader in blood-based circulating tumor DNA (ctDNA) analysis and molecular diagnostics for oncology, today highlights results presented at the American Society of Clinical Oncology's Gastrointestinal Cancer Symposium (ASCO GI) comparing plasma KRAS mutation detection performance between two commercial liquid biopsy testing platforms, OncoBEAM™ RAS CRC and Idylla™ ctKRAS Mutation Test. In this study, conducted by a group of four leading Spanish hospitals that perform liquid biopsy testing in routine colorectal cancer (CRC) clinical practice, investigators found that OncoBEAM exhibited significantly higher detection of KRAS mutations compared to Idylla, especially at low allelic frequencies. Additionally, superior clinical sensitivity for KRAS mutation detection was observed for OncoBEAM versus Idylla when results were compared to standard-of-care tissue testing.

Sysmex Inostics launched the OncoBEAM RAS CRC CE Mark IVD Kit in 2016 as part of a global collaboration with Merck KGaA. OncoBEAM RAS CRC is a comprehensive digital PCR blood-based test which evaluates 34 mutations in KRAS and NRAS (RAS) as recommended by clinical practice guidelines to determine RAS mutation status in metastatic colorectal cancer (mCRC) patients prior to initiation of targeted therapy. In late 2017, Biocartis Group NV introduced a CE-marked RAS liquid biopsy test to run on the Idylla real-time PCR instrument. The performance of each assay has been directly compared to tissue RAS mutation testing methods. For example, several head-to-head performance comparison studies have shown that blood-based testing with OncoBEAM™ RAS CRC has demonstrated high concordance with tissue-based RAS testing methods. However, a direct comparison of RAS mutation detection on identical mCRC patient plasma samples has not previously been performed to investigate differences between results generated by the OncoBEAM and Idylla platforms.

As with any diagnostic test used in clinical practice to predict response to therapy, the demonstration of accurate clinical performance is of utmost importance. For example, the use of a RAS mutation test that lacks appropriate sensitivity may lead to mischaracterization of mCRC patients as wild-type (without a RAS mutation) and in turn may diminish patient response to anti-EGFR therapy, potentially leading to worse outcomes.  With the advent of new testing methods beyond tissue RAS mutation testing, clinicians and pathologists take extra care to consider real-world performance before employing in routine clinical practice.  In this manner, a group of pathologists and GI oncologists from leading hospitals and laboratories across Spain independently compared the mutation results obtained from testing mCRC patient plasma with OncoBEAM RAS CRC and Idylla ctKRAS.  

In the study, investigators compared the sensitivities of OncoBEAM and Idylla platforms for KRAS detection by submitting replicate plasma samples from 115 KRAS-positive samples previously determined by OncoBEAM to have mutant allele fractions of ≤ 5% to be run on the Idylla ctKRAS platform.  Mutant allele fraction (MAF) represents the proportion of mutant DNA molecules present in a sample at the time of blood draw and is associated with the clinical sensitivity of liquid biopsy assays. In 115 patient samples determined by OncoBEAM to have a KRAS mutation at MAF ≤ 5%, Idylla ctKRAS detected KRAS mutations in 81 samples, resulting in a positive percent agreement (PPA) of 70.4%.  In samples with MAF values ≤1%, the PPA decreased to 61.2%, and in samples  ≤ 0.1%, positive percent agreement of Idylla results to those of OncoBEAM decreased to 41.2%, showing a significant drop in sensitivity below these critical clinical thresholds.  

Testing with Idylla was also compared in a cohort of 43 patients with KRAS mutations detected by tissue testing and plasma MAF values determined by OncoBEAM to be ≤ 1%.  In this group of 43 patients, which account for 37% of total pool from the trial, OncoBEAM demonstrated 72.1% concordance with tissue results, whereas Idylla demonstrated 46.5% concordance with KRAS tissue results. The studies concluded that OncoBEAM demonstrated greater clinical sensitivity for plasma detection of RAS mutations than Idylla. These results have important clinical implications, as a test with diminished sensitivity can have significant impact on the accurate identification of patients that may benefit from the administration of targeted therapy.    

Dr. Ana Vivancos, Principal Investigator, Cancer Genomics Group at Vall d'Hebron Institute of Oncology (VHIO) in Barcelona commented on the findings, "We were quite surprised by the results of this comparison which showed a great disparity in plasma RAS mutation detection performance between Idylla and OncoBEAM.  The results reveal unequivocally that the use of a highly sensitive assay like OncoBEAM for plasma RAS testing delivers more accurate results than Idylla. For example, in 31 patients which had a KRAS mutation by tissue testing, OncoBEAM detected a KRAS mutation in all 31 plasma samples, however, Idylla only detected a KRAS mutation in 14 of the 31 replicate plasma samples. Importantly, these results show a gray area where real-time PCR based assays like Idylla show reduced RAS mutation detection accuracy in plasma as compared to tissue testing and digital PCR testing with OncoBEAM.  This should serve as a reminder that not all liquid biopsy assays are equivalent and clinicians and molecular biologists need to be aware that assays lacking appropriate sensitivity may result in diminished precision to guide targeted therapy."

Additional information on poster details can be found below and can be accessed at https://www.asco.org/2018-gastrointestinal-cancers-symposium.

Presentation Details (all times local):

• Saturday, January 20 Level 1 - West Hall 066, 7:00am-7:55am and 12:30pm-2:00pm, BOARD B19 (Abstract 592) poster session C (Cancers of the Colon, Rectum, and Anus), Evaluation of the sensitivity of RAS mutation detection of the Idylla platform in comparison to the OncoBEAM RAS CRC assay. A. Vivancos, E. Aranda, M. Benavides, E. Elez, A. Gomez, M. Toledano, M. Alvarez, M. C. Parrado, V. García-Barberán, E. Diaz-Rubio.

About OncoBEAM™ 

Sysmex Inostics' highly sensitive OncoBEAM™ assays allow for molecular genetic analysis of cell-free tumor DNA from blood or plasma, delivering an individualized approach to complement treatment decision-making in oncology. Based on the highly sensitivity BEAMing technology developed at the Johns Hopkins University School of Medicine, OncoBEAM™ testing is able to provide multiplex hotspot mutation analysis for the accurate and reliable detection of rare mutant molecules of tumor DNA from blood samples of patients with cancer.  Due to its minimal-invasive nature, OncoBEAM™ delivers new possibilities for cancer management while minimizing costs and risks inherent with tissue biopsies. The OncoBEAM™ assays target a wide variety of clinically actionable genetic mutations in various cancers like melanoma, colorectal, breast and lung cancer, delivering information in real-time to support therapy selection, detection of emergent mutations and assessment of drug response. In the US, OncoBEAM™ tests are available as GCP and CLIA services. OncoBEAM™ RAS CRC CE IVD kit is available in EU.

About Sysmex Inostics 

Sysmex Inostics, a subsidiary of Sysmex Corporation, is a molecular diagnostic company whose core competency is mutation detection utilizing highly sensitive technologies such as BEAMing and a proprietary Plasma-Sequencing approach. Sysmex Inostics is a trusted partner to leading pharmaceutical companies, advancing their efforts to bring the most effective personalized cancer therapies to global markets.

With BEAMing being one of the most sensitive technologies available today for the detection of tumor specific somatic mutations in blood samples, Sysmex Inostics' OncoBEAM™ services are readily available to support clinical trials and research in oncology. Furthermore, Sysmex companion diagnostics (CDx) team offers services for the development of non-invasive cell-free DNA-based IVD tests supported by a growing network of partners to cover the entire IVD development process. In addition, OncoBEAM™ tests are available through a CLIA certified laboratory for routine clinical analysis.

Sysmex Inostics' headquarters and GCP Service Laboratory are located in Hamburg Germany; Sysmex Inostics' CLIA certified and GCP Clinical Laboratory is located in Baltimore, Maryland; Sysmex Inostics' Commercial Offices are located in Mundelein, IL. For more information on OncoBEAM™ blood testing and the BEAMing technology refer to www.sysmex-inostics.com or email [email protected]

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