The Clinical Value of Sysmex Inostics’ OncoBEAM RAS CRC Assay Highlighted in Back-to-Back Studies Published in the Annals of Oncology

Date: 2017-07-19 Tags: Press release

Mundelein, IL, 2017.07.19 – Sysmex Inostics, a subsidiary of Sysmex Corporation, a global leader in blood based circulating tumor DNA (ctDNA) analysis and molecular diagnostics for oncology is pleased to announce new data from two prospective-retrospective studies recently published back-to-back in the Annals of Oncology highlighting the important clinical value of blood-based RAS mutation detection for the management of metastatic colorectal cancer patients (mCRC).  Both studies utilized Sysmex Inostics’ OncoBEAMTM RAS CRC assay which was granted CE Mark approval in 2016 as part of a global collaboration with Merck KGaA.  OncoBEAMTM RAS CRC is a comprehensive blood-based test which evaluates 34 mutations in KRAS and NRAS as recommended by clinical practice guidelines to determine RAS mutation status in mCRC patients prior to initiation of targeted therapy.
 
Both groups performed testing at their respective centers of excellence certified to run the OncoBEAMTM RAS CRC assay in Spain, including, Vall d'Hebron Institute of Oncology, Hospital del Mar, and the Health Research Institute of Santiago.  In both investigations, researchers set out to not only evaluate the degree of concordance of OncoBEAMTM RAS CRC plasma testing with RAS tumor testing, but to also take a clinically meaningful step forward by performing independent direct treatment related outcome comparisons of RAS mutation detection in plasma versus tumor tissue to inform therapy decisions.
Clinical investigators from Hospital Del Mar and the Health Research Institute of Santiago evaluated the concordance of results in plasma tested with OncoBEAMTM RAS CRC and tissue tested by standard-of-care methods procedures1.  The overall concordance between tumor testing and OncoBEAMTM RAS CRC plasma testing was 93.0% in 115 mCRC patients recruited from the two Spanish hospitals. A key finding was that the progression-free survival (PFS) for wild-type RAS patients as determined by tissue testing and for wild-type RAS patients as determined by plasma testing was identical (10.3 months). The investigators concluded that the high overall agreement between baseline plasma and tissue RAS mutation status and identical response to subsequent therapy demonstrates the utility of blood-based testing with OncoBEAMTM RAS CRC as a viable alternative to tissue standard of care (SOC) for determining RAS mutation status in mCRC patients treated in routine clinical practice.  

With the OncoBEAMTM RAS CRC assay firmly established as a surrogate for tissue testing, the investigators then sought to evaluate the assay’s potential role for monitoring response and resistance during treatment. They found that in patients with RAS mutant tumors, RAS plasma mirrored clinical and radiological response to treatment with chemotherapy drugs and was an early predictor of response.   Moreover, use of the assay showed potential in evaluating response to antiangiogenic drugs with investigators envisioning its use as a complement to radiological assessment of response.
As part of their research, investigators aimed to assess the prognostic value of the RAS mutant allele fraction (MAF) or the fractional abundance of mutant DNA alleles relative to wild-type DNA alleles in a plasma sample.  Evaluation of basal MAF levels in a cohort of 22 patients with at least 3 year of follow-up revealed a strong prognostic indication as patients with MAF levels ≥1% had significantly lower PFS and OS than those with basal levels <1%.

Similarly, in a cohort of patients undergoing treatment with anti-EGFR therapy longitudinal monitoring of plasma revealed new RAS mutations in 39% of patients at the time of acquired resistance to anti-EGFR treatment.  Importantly a significant number of patients had a RAS mutation detected below 0.1%, which speaks to the requirement for a highly sensitive assay to monitor molecular signals of acquired resistance.  “Throughout the continuum of care of mCRC patients, from initial diagnosis through disease progression, the accuracy and reliability of blood-based testing is vastly improved with a highly sensitive assay such as OncoBEAMTM” says Dr. Clara Montagut, senior author of the study.  
In a parallel study led by Ana Vivancos of the Vall d’Hebron Institute of Oncology, Barcelona, Spain, investigators set out to evaluate the accuracy of OncoBEAMTM RAS CRC to determine plasma RAS mutation status as compared to standard of care tissue testing in a cohort of 146 mCRC patients2.  This study represents the first clinical series showing the usefulness of detecting ctDNA RAS point mutations in the largest cohort of patients thus far and performed locally in a general hospital with the OncoBEAMTM RAS CRC workflow. Patients representative of routine clinical practice were included with almost equal representation of newly diagnosed, treatment naïve patients and those that had received a range of treatments except for anti-EGFR therapy.  Results demonstrated a high overall concordance of close to 90% between standard of care real-time PCR tumor testing and OncoBEAMTM RAS CRC plasma testing.  

In a closer examination of patients for which mutations were detected in the plasma but not in corresponding tissue by standard of care techniques, re-evaluation by tissue BEAMing revealed low frequency mutations in the tissue of roughly half of these patients.  Further examination of metastatic tissue sites in some patients revealed the same mutation as that determined in the plasma but not present in the primary tumor tissue. This again highlights the utility of a highly sensitive plasma assay to capture tumor molecular heterogeneity and overcome limits of standard of care tissue testing in patients with metastatic disease.  
A key finding of this study was the comparison of outcomes based on SOC tissue plasma RAS testing. Similar median PFS was observed for wild-type patients determined by tumor tissue testing and RAS wild-type patients by OncoBEAMTM RAS CRC who received anti-EGFR plus irinotecan therapy in the second- or third-line setting (8.9 months and 8.7 months, respectively).   Further, this study supports the prognostic value of the fraction of circulating RAS mutations with patients having a RAS MAF value less than 10% experiencing a median overall survival (OS) of 27.8 months, versus those with RAS MAF values above 10% having a median OS of 16.4 months. A closer analysis of RAS MAF values also revealed that 48% of patients had a circulating levels of RAS mutations less than 1%, thus supporting the clinical requirement of a highly sensitive assay like OncoBEAMTM RAS CRC to accurately determine plasma RAS mutation status.  

As Dr. Ana Vivancos, senior author and lead investigator remarked, “There is no question that a highly sensitive assay delivers clinical accuracy and reliability and is vital for the routine management of patients with metastatic colorectal cancer.  We initially thought that the proportion of circulating RAS mutations would be much higher, given the degree of disease dissemination in mCRC patients.  However, we were somewhat surprised by the finding that roughly half of patients had such low levels of circulating RAS mutant ctDNA copies.  This is important as it provides evidence that the routine use of a plasma based tumor DNA assay requires high sensitivity such as that exhibited by OncoBEAMTM RAS CRC to accurately classify the full spectrum of patients with advanced colorectal cancer.”
1.    Vidal, J. et al. Plasma ctDNA RAS mutation analysis for the diagnosis and treatment monitoring of metastatic colorectal cancer patients. Ann. Oncol. Off. J. Eur. Soc. Med. Oncol. (2017). doi:10.1093/annonc/mdx125
2.    Grasselli, J. et al. Concordance of blood- and tumor-based detection of RAS mutations to guide anti-EGFR therapy in metastatic colorectal cancer. Ann. Oncol. Off. J. Eur. Soc. Med. Oncol. (2017). doi:10.1093/annonc/mdx112

About OncoBEAM™

Sysmex Inostics highly sensitive OncoBEAM™ services 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.

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 Plasma-Sequencing and BEAMing. 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 Inostics 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 are located in Mundelein, IL; Sysmex Inostics’ Clinical Laboratory is located in Baltimore, Maryland; Sysmex Inostics’ Service Laboratory is located in Hamburg, Germany. For more information on OncoBEAM™ blood testing and the BEAMing technology refer to www.sysmex-inostics.com or email info@sysmex-inostics.com.

 


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