Study shows that an individual's response to immunotherapy can be predicted within weeks, based on increasing or decreasing levels of circulating tumor DNA.
A test that detects changing levels of tumor fragments in the blood may offer a less invasive way to determine who will benefit from immunotherapy. Although the treatment approach can shrink tumors and prolong survival for patients with advanced cancers, only up to 30% of patients benefit from it, according to researchers at the University Health Network.
Predicting which patients would benefit can be crucial because of the severe potential adverse effects and knowing whether to begin or continue treatment would be helpful when weighing different options. Investigators addressed this issue by evaluating the responses of various patients with cancer to a specific immunotherapy drug via a customized test based on each patient’s tumor profile.
Based on these tests, the investigators found that an individual’s response to the treatment can be predicted within weeks, based on increasing or decreasing levels of circulating tumor DNA (ctDNA) fragments shed from the tumor into the blood. They noted that a decrease in the circulating tumor DNA fragments at 6 to 7 weeks after treatment with pembrolizumab was associated with a beneficial response and longer survival.
The study included 74 patients with different types of advanced cancers, all of whom were treated with pembrolizumab. In order to customize the tests, all the genes from the tumor biopsy tissue of each patient were sequenced or decoded, with specific attention on the mutations that occur in cancer. According to a press release, these mutations ranged from dozens to tens of thousands of mutations per tissue sample.
After this process, 16 genetic mutations for each patient were selected to develop a specific test and were customized to detect personalized ctDNA of each patient via a blood sample.
“When we looked at all 20,000 genes in each cancer, the range of mutations in different individuals was huge due to the many different cancer types in the study,” said co-senior author Trevor Pugh, PhD, FACMG, in a statement. “The novelty is that, rather than taking a one-size-fits-all approach, we designed a personalized blood test for each person based on their own cancer’s mutation list.”
Of the 74 patients, 33 had a decrease in ctDNA levels from their original baseline levels to weeks 6 to 7 after treatment with the drug. These 33 also had better treatment responses and longer survival. Notably, all 12 patients who had clearance of the ctDNA to undetectable levels during treatment were still alive at a median follow-up of 25 months.
“Few studies have used a clinical biomarker across different types of cancers,” said co-senior author Lillian Siu, MD, FRCPC, in a statement. “The observation that ctDNA clearance during treatment and its link to long-term survival is novel and provocative, suggesting that this biological marker can have broad clinical impact.”
A blood test could predict who benefits from immunotherapy [news release]. University Health Network; August 3, 2020. https://www.uhn.ca/corporate/News/PressReleases/Pages/blood_test_could_predict_who_benefits_from_immunotherapy.aspx. Accessed August 10, 2020.