EGFR-Mutated NSCLC: Are Frontline Combinations the Future? - Episode 2

Metastatic NSCLC: The Role of Liquid Biopsy


John V. Heymach, MD, PhD: We have liquid biopsies that are available. When and where do you use the liquid biopsies? Will you do it up front for patients, or do you do it if there’s not enough tissue? How are you using it? Is there any resistance?

Edgardo S. Santos Castillero, MD, FACP: For the liquid biopsy, John, the technology came to the United States at the end of 2014. I started to use it at the same time. I was sending tissue and liquid biopsy simultaneously for many reasons. At that time in 2014, and still in some places, there was still this rule for Medicare patients: If they get a biopsy at a hospital, that hospital cannot send the biopsy until after 14 days after the procedure. There’s a lot of time that we are losing, and the patient with stage IV lung cancer is waiting for us to know. That’s why I decided at that time to send a liquid biopsy because, on the first visit of the patient to your clinic, you’re able to send that blood test, and you may have an answer quickly. Now, I remember when I sent my first liquid biopsy: It was about 2 weeks. Now you can get an answer from 3 to 7 days, and you may have an entire profile that will help you start therapy right away if you find a specific driver mutation. The answer for you is that I’ve been using that at the same time.

As time passed, a colleague of ours from a different institution also proved in a prospective trial that both of those technologies, using NGS [next-generation sequencing] in the tissue and NGS in the blood, are complementary and are more exclusive. Perhaps some of them missed the driver mutation that we are looking for because we need to remember that, No. 1, no technology is perfect. There is tumor heterogeneity depending on where you do the biopsy, and it is also so in the liquid biopsy: the same thing happens. A liquid biopsy is great if you have the DNA of the tumor circulating in the blood, but if the tumor is not shedding tumor cells to the circulation, you will not find the mutation regardless of whether you have the best technology. None of those technologies or labs, either tissue or plasma, is perfect. Both work together.

John V. Heymach, MD, PhD: Yeah, I agree with you. The study, there was 1 that you mentioned from UPenn [the University of Pennsylvania], in which they showed that, if you send both, you find out that tumor biopsies alone miss something like 10% of cases. If you think you’re covering everything with tumors, you’re not: There’s some you could be missing. There is a good argument for sending both of them, and you’ll be getting it quicker. I can say that, at The University of Texas MD Anderson Cancer Center, we’re a big cancer center, but it still takes a long time between ordering the biopsy and getting the patient scheduled. They then get the biopsy, and sometimes, the tissue is not sufficient, and you can waste a few weeks on that.

Edgardo S. Santos Castillero, MD, FACP: Absolutely.

John V. Heymach, MD, PhD: With plasma, at least it is in our hands. We’re able to detect drivers in something like 80% to 90% of the cases if they’re there.

Edgardo S. Santos Castillero, MD, FACP: Yeah. Another thing that we haven’t mentioned, John, is the concordance between the 2: It’s like 98% concordance. If the problem is in the blood, you know that it will be in the tissue, so this is important.

John V. Heymach, MD, PhD: Yeah. That’s been our experience as well. We recently reported this: If it’s a positive test by plasma, you can have a high degree of confidence because the positive predictive value of the blood test is extremely high, but if the blood doesn’t come up with anything and your suspicion is still high, let’s say it’s in a nonsmoker or a younger patient, it’s probably important to wait for the tumor tissue as well.

Edgardo S. Santos Castillero, MD, FACP: Absolutely. Totally.

Transcript Edited for Clarity