Microsatellite instability (MSI)/mismatch repair deficient (MMR) tumors are rare in patients with pancreatic ductal adenocarcinoma, but its status may have significant implications for treatment, according to a recent study
published in Clinical Cancer Research.
After examining samples from 833 patients, researchers found that seven patients had MSI/MMR deficient tumors occurring at a frequency of about 1 percent.
All seven patients were found to have Lynch Syndrome, which is an inherited disorder caused by genetic mutations that increase a person’s risk of developing certain cancers including colon, endometrial, small bowel, gastric, ovarian, urinary tract and pancreatic.
“Pancreas cancer is an increasingly common malignancy and over 54,000 individuals in the United States will be diagnosed with this cancer in 2018,” said Eileen M. O'Reilly, M.D., associate director of the David M. Rubenstein Center for Pancreatic Cancer at Memorial Sloan Kettering Cancer Center and professor of medicine at Weill Cornell Medical College, both in New York City, said in an interview with CURE
“There have been significant developments in our underpinnings for the development of pancreas cancer on both a molecular and genetic basis.”
In the study, four patients (57 percent) with MSI/MMR deficient tumors were treated with immune checkpoint inhibitor therapy, which involves a drug that blocks certain proteins made by some types of immune system cells, like T cells. One patient experienced a complete response, two had partial responses and one had stable disease.
“This is the one important, although rare, setting in pancreas cancer where immune therapy may have a major role,” said O’Reilly. “Studies have shown that individuals with this finding have a high chance of benefitting from this type of therapy.”
Keytruda (pembrolizumab), a checkpoint inhibitor, was approved by the Food and Drug Administration in March 2017 for the treatment of adult and pediatric patients with unresectable or metastatic solid tumors that are MSI/MMR deficient. This study included several patients with pancreas cancer, noted O’Reilly.
Testing for MMR deficiency can be done one of three ways, explained O’Reilly, including staining the tumor directly for loss of certain proteins; by evaluating the DNA for “microsatellites” or by sequencing the tumor, called next generation sequencing (NGS); and looking for the cumulative DNA changes that are present.
“Increasingly in pancreas and other malignancies where there is a limitation on available tissue, NGS and bioinformatics approaches are used to evaluate for MSI as they provide this information and other important information that may be relevant from a therapeutic perspective,” she said.
O’Reilly added that this information is important for patients and their families to know and understand.
“Testing should be considered in the appropriate clinical context with a recommendation for patients with pancreas cancer that this be undertaken by NGS approaches given the additional information that may be gleaned from such testing,” she added.