A study of nearly 1,000 samples showed that Guardant Health’s blood test was able to determine microsatellite instability status about as accurately as tissue-based biopsies, potentially providing an easier way to predict a cancer patient’s response to immunotherapy across multiple types of solid tumors.
Known as MSI, the genetic biomarker serves as evidence that the body’s mechanism for fixing small errors in DNA is not functioning correctly, leaving them more vulnerable to cancer-causing mutations.
In advanced cancer patients, people with high amounts of instability have been found to respond well to PD-1 and PD-L1 immune checkpoint inhibitors—such as Merck’s Keytruda immunotherapy, the first cancer treatment approved based on a patient’s MSI or mismatch repair deficiency status as opposed to where in the body the tumor originated.
“Unfortunately, less than half of all advanced colon cancer patients are tested for this important biomarker,” Jeeyun Lee, M.D., Ph.D., an associate professor in the Division of Hematology/Oncology at Samsung Medical Center in Seoul, South Korea, said in a statement.
MSI-high status occurs most frequently in colorectal, endometrial and gastroesophageal cancers, according to Guardant, though overall incidence is about 1% of cases. That rarity, in addition to a lack of available biopsy tissue not used for other tests, can contribute to a lack of routine MSI testing.
“Across all solid tumors, we suspect the testing rate is far lower, in part due to challenges of working with tissue samples,” Lee said. Results of the study, involving researchers from Guardant, MD Anderson Cancer Center, the Samsung Medical Center and other institutions, were published in Clinical Cancer Research, a journal of the American Association for Cancer Research.
Researchers compared 949 evaluable patients with 40 distinct cancer types using the Guardant360 blood test and standard tissue biopsies, finding an overall accuracy of 98.4%. The liquid biopsy identified 87% of patients previously reported as MSI-high, and 99.5% previously reported as MSI-low or microsatellite-stable.
They also found that a small cohort of 16 MSI-high patients with metastatic gastric cancer identified with Guardant’s test saw an objective response rate of 63% and a disease control rate of 81% when treated with checkpoint inhibitors, on par with those who underwent tissue testing.
“Millions of microsatellites exist throughout the genome, but most of them are poorly suited for blood-based clinical genomic analysis,” said co-author Scott Kopetz, M.D., Ph.D., an associate professor of gastrointestinal medical oncology at the University of Texas.
The chromosomal positions associated with MSI include highly repetitive genomic sequences, which typically make detection difficult when analyzing the shorter fragments of circulating tumor DNA found within the bloodstream.
“By adding MSI testing into a noninvasive screening panel, clinicians can routinely scan for this prognostic factor without ordering a separate test,” said Kopetz.