Liquid Biopsy Advances: Vital Role in Biomarker Testing in Lung Cancer

Clinicians and patients need to understand that it’s medically important to not start the wrong therapy, explained David P. Carbone, MD, PhD, director, Thoracic Oncology Center; professor of internal medicine; and coleader of the Translational Therapeutics Program at The Ohio State University in Columbus. He is also president of the International Association for the Study of Lung Cancer.

In the third, and final, part of our interview, Carbone acknowledges that although biomarker testing can be an overwhelming process to understand and liquid biopsy is not 100% sensitive, it can both provide survival advantages on its own and augment patient outcomes following chemotherapy and radiotherapy.

Transcript

How has biomarker testing, and particularly liquid biopsy, evolved over the past decade?

There's a lot of challenges to biomarker testing, and it's evolving at a very high speed. We're adding new targets—we recently added KRAS as a targetable abnormality—and the testing, I think, has become more streamlined. We've learned how to do adequate biopsies for testing. But sometimes biopsies aren't adequate for testing. A patient gets a biopsy that's diagnostic of cancer, and they don't have enough tumor there to do the biomarker testing, and in those cases, we'll often schedule a rebiopsy. But while we're waiting for that, we now have the tool of the liquid biopsies, which you mentioned, and these actually tend to come back faster, 5 to 7 days, and have become quite good.

It's pretty amazing that you can take a tube or 2 of blood and that with advanced technologies, you can detect tiny amounts of DNA that's shed by cancers into the bloodstream, and not only detect it, but sequence it and determine the presence or absence of these driver abnormalities. The problem is, it's not 100% sensitive—even the tissue biopsy’s not 100%—liquid biopsies can miss drivers.

So, in my practice, we still rely mostly first on the tissue biopsy, but liquid biopsy is maybe 70% or 80% sensitive, and if we get a driver mutation result from our liquid biopsy, that's good enough. We don't need to look further and we act on that, and those patients do well. So this is a very important new technology that we use every day.

What strategies can improve patient education on biomarker testing?

The whole process is intimidating. Can you imagine going about your normal life, then you have a little bit of a pain or a cough or something, and then they find you have advanced lung cancer, and your whole life changes? You're learning a new set of terminology. You're getting tests done that you don't know what they are. You're seeing a bunch of doctors that you've never seen before, and they're telling you stuff that you don't really understand. There's a stress involved in that that results in many people wanting to start treatment right away. “I have to start treatment today!” You can't get biomarker testing back in a day in general.

So, it's important for clinicians and patients to understand that it's better to do the right thing than the convenient thing and sometimes you can do absolutely the opposite wrong thing by randomly choosing a therapy and not waiting for biomarker testing. Unfortunately, in this country, not everyone gets biomarker testing, and for those that have it ordered, often it's not acted on, they get the wrong therapy in spite of biomarker testing, or they get started on the wrong therapy before the biomarker testing comes back.

And almost always, these cancers develop over months or years, and so waiting 2 weeks for a biomarker test, even though it's psychologically stressful, really is hugely medically important so you don't do the wrong thing and start the wrong therapy—which could be not only costly, but result in toxicity that could have been avoided if you had had the right therapy from the beginning.

What is most important to know about biomarker testing in lung cancer?

The most recent approvals for targeted therapies, based on biomarker testing, are in the early-stage setting in patients with resectable tumors. And I think there's still a learning curve going on in those patients and surgeons, especially, who are not used to doing biomarker testing for patients who have stage II or resectable stage III disease. Right now, neoadjuvant and adjuvant immunotherapy is FDA approved—dramatically effective at improving survival outcomes after surgery—and targeted therapies are approved, both for EGFR and for ALK after resection.

Using immunotherapy in an EGFR-mutant patient would be the wrong thing to do, and so the one message to be conveyed today is really to educate thoracic surgeons and patients, even if you have a stage II lung cancer that surgeon says I can take it out on Tuesday. Really, you should ask the surgeon to do biomarker testing and get that result back to make sure you're not missing an opportunity to improve outcomes from surgery or chemo/radiation for stage III, because these options dramatically improved progression-free survival and overall survival, and it's a shame to miss them.