Researchers have demonstrated recently that the Guardian360 assay can accurately detect MSI, an important biomarker used to predict response to immunotherapy regardless of tumor type.
For patients with advanced cancer, MSI is a good predictor of response to immunotherapy with PD-1 and PD-L1 inhibitors in multiple tumor types. It has been reported to occur in about 1% of cases, and any patient with advanced cancer who is found to be MSI-High is eligible for treatment with immunotherapy. MSI-High occurs most frequently in colorectal, endometrial, and gastroesophageal cancers.
“Unfortunately, less than half of all advanced colon cancer patients are tested for this important biomarker. And across all solid tumors, we suspect the testing rate is far lower, in part due to challenges of working with tissue samples,” said Jeeyun Lee, MD, Associate Professor, Division of Hematology/Oncology, Samsung Medical Center. “By incorporating these results into a simple blood test, we should be able to increase the number of patients who get this information and benefit from appropriate immunotherapy.”
The validation of MSI detection methods of Guardant360 is an important achievement in the development of liquid biopsy technology. Chromosomal positions most often associated with MSI are made up of highly repetitive genomic sequences. Accurately mapping circulating tumor DNA (ctDNA) fragments to the genome requires innovation in panel design, DNA capture, and bioinformatics analysis, because the fragments are generally much shorter than tissue-derived tumor DNA.
In order to validate the MSI detection of Guardant360, researchers compared the results of 1,145 Guardant360 samples to MSI status determined using standard-of-care tissue testing results taken from medical records. The results from Guardant360 were the same as the standard-of-care tissue test in 98.4% of cases.
Also, it is the first report of immune checkpoint inhibitor therapy outcomes in plasma MSI-High patients. In a cohort of 16 MSI-High gastric cancer patients treated with immune checkpoint inhibitors, the objective response rate was 63% and disease control rate was 81% consistent with responses for patients identified by tissue testing.
“Millions of microsatellites exist throughout the genome, but most of them are poorly suited for blood-based clinical genomic analysis,” said Scott Kopetz, MD, PHD, and Associate Professor of Gastrointestinal Medical Oncology at The University of texas and co-author on the study. “These results show that a carefully designed panel, combined with efficient DNA-capture biochemistry and sophisticated bioinformatics tools, allow for accurate, sensitive MSI detection.”
“We are proud to be able to bring this innovation to Guardant360 ordering physicians and the patients they treat,”said AmirAli Talasaz, PhD, Guardant Health Co-Founder and President. “We remain committed to improving the performance and utility of our products as our lab and the broader oncology field achieve advances in technology and breakthroughs in treatment.”