Abstract
Liquid biopsies seem to have come into their own in recent years. These are tests done on a blood sample to detect cancer cells from a tumor. The premise is that these cancer cells circulate in the blood, or at least snippets of DNA from tumor cells circulate in the blood. Evidence is being gathered to determine whether a liquid biopsy can detect cancer at an early stage, help to determine which treatment is appropriate, and or whether treatment is working and whether cancer has reoccurred. This less invasive method has the benefit of being able to be done multiple times over the course of an individual's disease journey.
There are a number of companies and academic institutions working to establish reliable tests. For example, investigators from MD Anderson are testing Guardant Health's Guardant360 assay. According to an abstract they released recently, 1 they have tested a total of 282 patients with nonsmall cell lung cancer (NSCLC), a tumor type that is typically used in precision medicine, and now liquid biopsy experimentation. Liquid biopsy offers an opportunity to test tumors that might be inaccessible otherwise.
These tests often have a shorter turnaround time than tissue biopsies. But even if they are more accessible and if they are quicker, initial wariness considered whether liquid biopsies could detect mutations at all. That question has been settled. How well they detect them is now more of a concern, and ultimately the question of whether these tests improve patient outcomes is critical. Clinical utility is how the laboratory community would describe this, and clinical usefulness is what some patients have described as the gold standard. Is this useful to us? Does it improve patient outcomes?
Other academic groups and companies have been working in the same vein. UPenn is working with Guardant. Resolution Biosciences did studies in the United States and Australia, and published in November, showing that its test could rapidly detect mutations in a majority of NSCLC cases, including individuals whose tissue could not be successfully tested. 2
In a wonderful milestone, another liquid biopsy company, Inivata, reported that Medicare administrative contractor Palmetto GBA has granted a final decision to provide specific coverage for its test for all fee-for-service Medicare patients in the United States with advanced NSCLC who meet other criteria as well. 3 Their test, InvisionFirst will receive reimbursement when genotyping results for EGFR, ALK, ROS1, and BRAF variants are not available and when tissue-based comprehensive genetic profiling (CGP) is deemed infeasible. Some of these other criteria include considering patients on, or after, chemotherapy, immunotherapy, and/or EGFR tyrosine kinase inhibitors who have never been tested for those biomarkers, and for whom tissue-based CGP is not possible, or for patients progressing on EGFR tyrosine kinase inhibitors. There are a few other technical wrinkles. And the determination also states that clinicians should still consider tissue genotyping if no genetic alteration is detected by the InVision test.
Inivata provided a large-scale prospective clinical validation study led by researchers at the Washington University School of Medicine, and showed that the liquid biopsy test had high agreement with standard of care tissue profiling, enabled more complete profiling, and detected 26% more actionable mutations than tissue analysis.
Cancer is the second leading cause of death. Improving diagnosis, the time it takes, and its precision, is critical in the age of personalized medicine. Additionally, if liquid biopsies are reliable and they offer a way to provide more targeted therapies, they will greatly enhance the arsenal of tools.
As with any technology resulting from clinical trials, there are some critical societal issues. Will these assays be accessible, including affordable? Medicare coverage can certainly make a big difference in paving the way to availability and accessibility. And, how can we collectively as a society increase patient engagement and participation, such that trials enroll more quickly and efficiently, people understand the value of the trial, and are true partners in the endeavor.