Liquid Biopsies: Complementary Tool in Detecting Driver Mutations in NSCLC

Sai-Hong Ignatius Ou, MD, PhD

Liquid biopsies can be used to augment tissue biopsies in non—small cell lung cancer (NSCLC), and in the case of insufficient tumor tissue, serve as the primary method of detecting a potentially actionable driver mutation with a faster turnaround time, explained Sai-Hong I. Ou, MD, PhD.

“All the commercial liquid biopsies across the United States can detect essentially all of the common driver mutations, such as EGFR-activating mutations, ALK, ROS1 fusions, BRAF V600E mutations, and even some of the driver mutations that have available clinical trials, such as RET fusions, NTRK fusions, EGFR exon 20 insertions, and HER2 insertions,” said Ou. “Liquid biopsy is going to take on a more prominent role as the primary method to detect actionable driver mutations.”

In an interview during the 2019 OncLive^® State of the Science Summit™ on Non—Small Cell Lung Cancer, Ou, health science clinical professor, Department of Medicine, Division of Hematology/Oncology, University of California Irvine School of Medicine, highlighted the conveniences of liquid biopsies relative to tissue biopsies, as well as current drawbacks to their use in detecting targetable alterations in lung cancer.

OncLive: What is the role of liquid biopsies for patients with targetable mutations?

Ou: In my practice, I'm seeing more patient referrals that come with liquid biopsies as a screening tool for targetable driver mutations in lung cancer. As we discussed in the State of the Science Summit™, tissue biopsy remains the gold standard. However, in certain cases, like if you have limited tumor tissue, liquid biopsy can be the primary method to detect actionable driver mutations.

The turnaround time is usually a little bit faster with liquid biopsy than what is seen with tumor biopsy. Most of the commercial liquid biopsies sequence fewer genes than tumor biopsies. With liquid biopsies, you can draw the blood and immediately send it to the commercial labs. With tissue biopsies, sometimes pathology labs will take some time to cut and stain slides before they send them out. It will usually add a few days of delay.

Do liquid biopsies have greater sensitivity in detecting certain mutations?

Right now, liquid biopsy is complementary to a tumor tissue biopsy. In terms of sensitivity, all the commercial labs tend to do a very good job of detecting all the driver mutations. It's not the technique that is the problem. The challenge is in patients who have very low tumor burden where you do not have enough tumor tissue or DNA shed to the blood to be detected; therefore, it's not the sensitivity of the assay per se. In cases where patients have a low tumor burden, such as patients with stage IV NSCLC who have a malignant pleural effusion or a small pulmonary nodule, you may not be able to detect the driver mutation. In most commercial labs, a certain cutoff is needed in order to call something positive. In most cases, they can detect the mutations, but it may not be enough by their own internal standard to say it’s a positive result. Next-generation sequencing is very sensitive. It's the nature of the disease that you are trying to detect.

Is there a preferred platform or assay that you recommend using?

Right now, I have seen many community practices using different platforms. I don't think it's my place to say which one is the best. We all have our own favorite commercial tests. [This decision] may also be dependent on the region, too. You need to be comfortable with what platform you're going to use, and if you have questions, you should be able to ask the company how to interpret the results.

What do you envision the future role of liquid biopsy to look like?

Liquid biopsies do not sequence as many genes as the tumor panel, which is why we can save time. In the future, the same number of genes are going to be sequenced by liquid biopsies as with tumor biopsies. In some of the commercial companies in China, the liquid biopsy offering is the same as the tumor biopsy offering in terms of number of genes and the nature of the mutation such as amplification or fusion. Eventually, we are going to have a uniform platform, whether it's tumor or liquid biopsy, in which the same number of genes and the nature of the mutations detected will be the same. That way, we won’t have to sacrifice knowing what is happening by using liquid biopsy.