A Simple Blood Test Is as Effective as a Biopsy in Detecting Lung Cancer Mutations

Biopsies are a necessary burden for people with cancer. Taking a small sample of tissue and sending it through genetic and molecular analysis can help doctors not just diagnose cancer, but also learn more about its inner workings to find the best treatments based on which mutations are feeding the disease.

But tissue biopsies are invasive, and depending on where the tumors are in the body, they can be painful to obtain. For some people, there may not even be enough cancer tissue for doctors to get the answers they need.

In a press briefing previewing the upcoming American Association for Cancer Research annual meeting in Atlanta, researchers reported that a commercial blood test, called a liquid biopsy, was at least as effective as a tissue sample at identifying important mutations in non-small cell lung cancers.

In a study funded by the manufacturer of the test, Guardant Health, 282 people at 28 centers in the U.S. with late-stage non-small cell lung cancer were tested both with Guardant’s liquid biopsy, called Guardant360, and their doctor’s choice of a tissue-based test to look for seven genetic markers in the tumors. Cancer experts have designated mutations in these markers as useful in guiding doctors to the appropriate therapies for attacking the cancer; a number of so-called targeted therapies designed to find and dismantle these mutations have been approved by the Food and Drug Administration (FDA) in recent years. Guardant 360 also looks for one genetic marker that can help to predict prognosis of these lung cancers.

The liquid biopsy was able to pick up these mutations at about the same rate as the tissue biopsies, which are currently the gold standard for testing. But the blood test also did so less invasively and took about half as long to produce results.

“This study shows that liquid biopsy is accurate and detects [markers] at the same rate as standard-of-care tissue testing of tumor tissue,” says Dr. Vassiliki Papadimitrakopoulou, professor of medicine at MD Anderson Cancer Center and lead author of the study. “This study gives us confidence that what is found in liquid biopsies really is what is found in the tumor.” (Papadimitrakopoulou serves on a number of advisory boards for pharmaceutical companies and received nominal fees as a consultant to Guardant in designing and running this trial.)

Guardant360 picks up fragments of DNA that tumors shed into the blood. In recent years, scientists have been working to isolate such cell-free tumor DNA, in order to make sure that they represent genetic material from just the tumor and not the patient’s DNA. The test is not currently approved by the FDA, but last year, the agency put it on the Expedited Access Pathway that would speed up approval, based on 20 studies the company has submitted. Guardant360, which can detect mutations in a number of genes known to be linked to a variety of solid tumors, is currently available in 30 countries, including the U.S., under a different regulatory scheme: as a laboratory-developed test. Doctors can order the test now, but if approved by the FDA, the test could become the first liquid biopsy to receive the agency’s green light, which would significantly expand the use of the test among clinicians.

In the study, tissue biopsies picked up at least one of the genetic markers in 60 people, and adding the liquid biopsy increased that number to 89: a 48% higher detection rate. The advantage of the blood-based test, says Papadimitrakopoulou, is not only that it provides results in about nine days compared to 15 days for the tissue biopsy, but also that it found markers in some people whose tissue biopsies were negative. It also found markers and potential targets for drugs in people who did not have enough tissue to test the traditional way.

Liquid biopsies represent a promising new strategy for improving cancer treatments. While this study did not follow the participants to track their outcomes, cancer doctors say that matching people to the right treatments sooner in their disease is an important way to potentially prevent or delay recurrences and help more people to live longer. The ease of the blood-based test could also make it possible to retest people when their cancers recur; in many cases recurrences are triggered when tumors become resistant to treatments, and retesting could help doctors identify new mutations that might be driving the cancer so that they can prescribe new, more effective therapies.

Papadimitrakopoulou also anticipates that the liquid biopsy will help more doctors who are caring for patients outside of major academic cancer centers to feel comfortable in making decisions about which drugs to use. The study included people from academic as well as community cancer centers. She says that about 30% of lung cancers can be treated with targeted therapies based on genetic markers in the tumors, but that such testing — whether using tissue biopsies or liquid biopsies — was only done in about 8% of people with non-small cell lung cancer. The results of the study, she says, should “allow more patients to access the right type of therapy for their tumors.”

Tissue biopsy remains the gold standard for genetically profiling a tumor in order to find the right targeted treatments. But if the results of this study are confirmed, liquid biopsies may become the first line of testing for more patients. Papadimitrakopoulou anticipates, for example, that people could be tested with a liquid biopsy and begin treatment based on the results; people whose liquid biopsy results are negative would then go on to get a tissue biopsy to confirm or provide more information than those results.

Guardant is also aiming to get FDA approval for diagnosing cancer in people with early-stage disease and is conducting other studies to explore how effectively the liquid biopsy can do that in a number of different solid cancers.