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Sysmex Inostics Validating Liquid Biopsies for Disease Monitoring

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NEW YORK (360DX) –  Sysmex Inostics is currently testing both of its liquid biopsy technologies for monitoring response to chemotherapy in breast cancer patients ­– one example in an overall effort by the company to explore the use of liquid biopsy tests to monitor disease progression across different types of cancers.

“I think in the next couple of years we will have almost reached a tipping point in terms of sheer data to show the decision points where circulating tumor DNA provides insight into what is going on with a patient’s tumor,” said Dan Edelstein, director of clinical marketing with Sysmex Inostics, a subsidiary of Japanese in vitro diagnostics company Sysmex. “One of the low hanging fruit for circulating tumor DNA assays is for therapy selection at different time points during tumor evolution, from diagnosis through progressive lines of therapy. However, fine-tuned monitoring [of] patients to detect and track residual disease, treatment resistance, and disease recurrence remains an area where the true clinical value of liquid biopsies has yet to be realized.”

Sysmex Inostics' breast cancer trial currently underway is a multiyear national test approved for the study of 225 patients across multiple institutions. The clinical trial is being conducted in partnership with researchers from Johns Hopkins University School of Medicine. While there have been numerous pilot tests using liquid biopsy to study disease progression, larger multi-institutional evaluations are necessary to demonstrate clinical utility in order to commercialize liquid biopsies for this use and make them available to all patients, Edelstein said.

Sysmex Inostics has two types of liquid biopsy, an OncoBEAM digital PCR (polymerase chain reaction) liquid biopsy, and a newer, next-generation sequencing liquid biopsy called Plasma-Seq, which uses PCR amplification on a next-generation sequencing platform. Both are being used in the breast cancer study. Plasma-Seq is being used for the gene TP53, which can have multiple mutations, because the technology allows for evaluating a larger breadth of mutations across genes.

The OncoBEAM digital PCR assay is being used to test for PIK3CA mutations because PIK3CA has only a few “hotspot” mutations and OncoBEAM’s high sensitivity and quick turnaround of results makes it well-suited for testing for targeted mutations, according to Dr. Ben Ho Park, medical oncologist and professor of oncology at Johns Hopkins School of Medicine specializing in breast and ovarian cancer.

Approximately one year into the study, the trial has enrolled approximately 50 patients, Park said. The trial is expected to last another year or two, with patients expected to come on board more quickly now that the trial is set up.

The trial measures whether patients who undergo neoadjuvant chemotherapy, to shrink or destroy tumors prior to surgery, still have circulating tumor DNA in their blood after the therapy but before the surgery, Park said. He anticipates that at least 95 percent of the time, when blood drawn following neoadjuvant therapy is clear of circulating tumor DNA, the patient no longer has cancer in her breasts, lymph nodes, or anywhere in her body. If successful, the trial could eventually allow patients to avoid surgery.

“We know that in breast cancer, and this is applicable to other kinds of cancer too, we are overtreating patients,” Park said. “We give chemotherapy to patients and probably 70 percent of those patients don’t need it, but we can’t define who has metastatic disease and who doesn’t.”

Sysmex Inostics has already begun to see data indicating the usefulness of liquid biopsy for disease monitoring in other types of cancer. For example, studies of RAS mutations in colorectal cancer have found that the amount of circulating tumor DNA, or the quantity of RAS mutations in a patient’s blood prior to therapy is highly prognostic of both progression-free survival and overall survival, according to Edelstein.

 “There is a definite need for a surrogate for tumor tissue to track and monitor patients through therapy,” Edelstein said. “There is a very real need to be able to detect after surgery or after chemotherapy whether there is any residual disease.”

Indeed, the use of liquid biopsies to predict cancer recurrence and to monitor earlier-stage patients for indications of tumors that may be spreading is gaining attention, though the efforts are still largely considered experimental. As a result, the clinical community remains uncertain how to view such technologies for patient care.

Some oncologists see liquid biopsy having the potential to be more effective than other existing methods of testing when it comes to monitoring disease progression.

“I think liquid biopsies look promising as far as unraveling the resistance mechanisms in a way that may ultimately be proven to be better than tissue biopsies,” says Dr. Wafik El-Deiry, a medical oncologist specializing in colorectal cancer and professor of hematology and oncology at Fox Chase Cancer Center in Philadelphia.

El-Deiry believes that liquid biopsies allows oncologists to get a more complete picture of the different types of mutations present in patients.

“There is already plenty of evidence from both clinical experience and and published reports that are pointing to this phenomenon where the liquid biopsy allows you to capture sampling from the different metastases and different tumor masses all shedding DNA into the blood,” he said. “Moreover, there is much more of this type of heterogeneity in patients who have been treated. Different parts of the tumor and different tumor metastases may evolve different resistance mechanisms and those can be reflected in the results of the liquid biopsy and may not be detected in the tissue biopsy. I think that’s what we are all realizing.”

Dr. Sumanta Kumar “Monty” Pal, a medical oncologist specializing in kidney, bladder and prostate cancer and codirector of City of Hope’s Kidney Cancer Program, said that he generally only orders liquid biopsies for patients who have already begun treatment.

“Very often there is a set pathway in which I will initially treat patients that wouldn’t necessarily be altered by the result of the liquid biopsy,” Pal said. “On the other hand, the liquid biopsy becomes useful after the patient has progressed beyond standard treatment in identifying new targets. I order it on multiple occasions in acknowledging that patients’ mutations are really dynamic they are not set. If you go through treatment A, B, and C, you can actually see a different liquid biopsy profile emerge that could alter the way in which you are treating the patient.”

Commercially, a handful of firms have also launched, or plan to launch, tests using liquid biopsy technology to monitor patients for early signs of cancer recurrence. They include Cynvenio Biosystems and CellMax Life.