Maximilian Diehn, MD, PhD
The use of next-generation sequencing (NGS) platforms and liquid biopsies in lung cancer could evolve to where these procedures are part of standard care, experts say.
“ctDNA assays are now in the clinic; they are here, they are not just in the realm of research anymore,” said Maximilian Diehn, MD, PhD. “For patients with lung adenocarcinoma [for whom you’re] looking at active EGFR
mutations or the T790M mutation, these are assays routinely being used in many centers to address patients who either can’t have biopsies in the frontline setting or try to minimize the number of biopsies you have to do. That is a very important thing we should be offering to our patients in the community.”
During the 2017 OncLive®
State of the Science SummitTM
on Advanced Non–Small Cell Lung Cancer, Diehn, an assistant professor in the Department of Radiation Oncology at Stanford Medicine, discussed the future of NGS platforms and liquid biopsies and his vision for them eventually becoming standard practice for patients with lung cancer.
OncLive: Your presentation covered NGS platforms and liquid biopsies. Can you provide an overview?
I focused my talk on a particular application of NGS related to the detection of ctDNA, which refers to fragmented DNA that can be found in the circulation of patients with cancer, and are becoming increasingly relevant in the research and management of patients with lung cancer.
I spoke about how we are currently using ctDNA in the clinic. There is a regulatory approved assay, particularly for EGFR
mutations related to patients with lung adenocarcinoma—where we can detect those now in the plasma or blood. We are using those in patients where we can’t perform a biopsy. For example, it’s too dangerous for the patient to have a biopsy, or they had a biopsy and there wasn’t enough tissue. So, we can consider using this test to determine whether they have activating mutations at the time of diagnosis and, if they are detectable, then the patient can get the EGFR
Also, more frequently, we are using these tests at the time of progression on EGFR
-targeted therapy because there is an FDA-approved drug osimertinib (Tagrisso) that targets the T790M mutation. If we can show that a patient developed T790M in the blood, then that is good [reason] to get the patient the drug. Then, we can avoid the need for biopsy at the time of progression by doing this blood test first.
In the second half, I talked about some of the emerging work that a number of groups are doing with applying NGS to detect ctDNA. The benefits of that approach are that you can detect and measure mutations in many genes at one time than just EGFR
. That opens up many new applications, including a very sensitive response assessment to see how patients are responding to treatments. It can potentially be used for determining if patients are cured or not after they have had surgery or local treatment. We can potentially use it some day in lieu of imaging as a way to follow our patients—just following up a blood test with patients rather than having to repeat scans all the time.
For the same kinds of patients for whom we’re using the T790M test clinically already, if we apply the NGS approaches like the one my lab developed, then we can show that many patients have multiple resistance mechanisms. That matters to how they perform when you treat them with a next line of therapy. In the future, we should be personalizing therapy potentially based on what mutations are appearing in a patient’s blood and selecting drugs based on that. Such studies are starting to be done.
We have seen a lot of data with liquid biopsies in recent years. What next steps would you like to see?
We need to do clinical studies that prove utility of applying these assays, so they can become part of the standard of care. One of the exciting, but also challenging, aspects of this field is that there are so many potential applications. But, if we want any one of those to be the standard of care, we have to show that it makes a difference to patient outcomes. Just because you can do it doesn’t mean it’s actually useful.