Liquid biopsies could help predict response to immune checkpoint inhibitors, according to researchers at the University of California San Diego. In a study published this month in Clinical Cancer Research they found that the number of alterations detected in the DNA collected from blood samples of cancer patients treated with immune checkpoint inhibitors was associated with response to the treatment.
"Immune checkpoint inhibitors are transforming cancer treatment; however, overall only about 20 percent of patients respond to these drugs, and the drugs sometimes have significant side effects," explained senior author Razelle Kurzrock, M.D., director of the Center for Personalized Cancer Therapy at the University of California San Diego Moores Cancer Cente.
“Most biomarkers used to predict response to checkpoint inhibitors are measured on tumor biopsy specimens and have limitations,” added lead author Yulian Khagi, M.D., a Hematology-Oncology fellow at the University of California San Diego Moores Cancer Center. "We wanted to identify an easily obtainable and easily interpretable biomarker that can predict response to checkpoint inhibitor therapy utilizing genomic sequencing of DNA that is shed from cancer cells into the bloodstream."
Using blood samples from 69 patients with different types of cancer treated with immune checkpoint inhibitor therapy, the investigators analyzed the ctDNA by next-generation sequencing. Specifically, they counted the number of variants of unknown significance (VUS, alterations/mutations in the DNA whose association with disease risk is unknown).
Of the 69 patients, 29% had more than three VUS alterations and 71% had three or fewer VUS in their ctDNA. After being treated with an immune checkpoint inhibitor, patients with more than three VUS in their ctDNA had significantly higher response rates (45%) compared with those who had three or fewer VUS (15%).
Among patients who had higher numbers of alterations of the VUS type, the median survival was not reached while those who had lower numbers of alterations of the VUS type had a median survival of only about 11 months.
"Our study demonstrated that high circulating tumor DNA [ctDNA, tumor DNA derived from a blood sample] alteration number was associated with response to checkpoint inhibitor therapy," Kurzrock said.
"Though the study was small, a significant difference could also be identified for a longer survival without progression of cancer and even a longer overall survival in the high versus low VUS alteration group," noted Khagi. "It is likely that, with larger studies, this difference will become more significant."