Two years ago, the Food and Drug Administration gave the first-ever approval to a drug to treat cancers based not on which tissues they affect, but on whether they carry a specific biomarker. Now, a study shows that it may be possible to detect the biomarker using a simple blood test.
Redwood City, California-based liquid biopsy firm Guardant Health announced Monday the publication of a study in Clinical Cancer Research, conducted by researchers at The University of Texas MD Anderson Cancer Center in Houston, the Samsung Medical Center in Seoul and at the company itself. The study found that the company’s Guardant360 assay was able to detect microsatellite instability-high (MSI-H) and mismatch repair deficiency (dMMR) status at a rate similar to that of standard tissue testing.
“Millions of microsatellites exist throughout the genome, but most of them are poorly suited for blood-based clinical genomic analysis,” said MD Anderson associate professor of gastrointestinal medical oncology and study co-author Dr. Scott Kopetz in a statement. “These results show that a carefully designed panel, combined with efficient DNA-capture biochemistry and sophisticated bioinformatics tools, allow for accurate, sensitive MSI detection.”
Shares of Guardant were down more than 4 percent on the Nasdaq Monday afternoon.
The researchers concluded that the cell-free DNA-based MSI detection with Guardant360 produced results highly consistent with those of tissue biopsy. The study was based on 1,145 cfDNA samples for which tissue MSI status based on tissue testing was available. In 949 samples, the overall accuracy was 98.4 percent, with a positive predictive value of 95 percent, with liquid biopsy detecting tissue MSI-H in 82 evaluable patient samples and microsatellite-stable status in 99.5 percent of 867. Additionally, among 16 patients with stomach cancer, 63 percent saw robust clinical activity of immunotherapy treatment.
The FDA approved Merck & Co.’s PD-1 checkpoint inhibitor Keytruda (pembrolizumab) for MSI-H and dMMR cancers in May 2017, meaning any solid tumor that displays either biomarker, regardless of where it occurs in the body. The first drug to win FDA approval solely for a biomarker-based indication, Loxo Oncology’s Vitrakvi (larotrectinib), received the agency’s green light in November 2018; Eli Lilly & Co. acquired Loxo in January for $8 billion.
Generally speaking, MSI-H is not a common biomarker. A 2017 study published in the Journal of Clinical Oncology, based on data from 11,139 tumor-normal tissue pairs across 39 cancer types, found MSI-H in 27 tumor types, with an overall prevalence of 3.8 percent.
However, the idea of liquid biopsy replacing tissue biopsy to find actionable biomarkers has met with some skepticism, particularly insofar as results from the former don’t necessarily match those of the latter. When another liquid biopsy company, Grail, presented data from one of its studies at the American Society of Clinical Oncology meeting in June, some experts said a false-positive rate even as low as 1 percent could be cause for concern. That, they said, could make it difficult for liquid biopsy to replace tissue biopsy if patients inevitably have to undergo both tests for confirmation. As such, they added, it would be ideal to use for certain high-risk populations, such as smokers.
Photo: CGToolbox, Getty Images