Liquid Biopsies May Ease Genomic Evaluation and Disease Management for NSCLC


For detecting genetic drivers and molecular aberrations in patients with metastatic non–small cell lung cancer, performing biopsies with comprehensive cell-free DNA, or liquid biopsies, may be a viable substitute for tissue-based biopsies. 

Mark Socinski, MD

Mark Socinski, MD

Mark Socinski, MD

For detecting genetic drivers and molecular aberrations in patients with metastatic non—small cell lung cancer (mNSCLC), performing biopsies with comprehensive cell-free DNA, or liquid biopsies, may be a viable substitute for tissue-based biopsies. To improve clinical evaluation for patients with mNSCLC, researchers in the NILE study set out to address the varying perceptions about the use of liquid biopsy over tissue genotyping, to prove that liquid biopsy is not inferior, and build on previous findings around NSCLC diagnosis.1

Conducting a liquid biopsy as a non-invasive alternative to surgical biopsy allows doctors to obtain a wide range of information about a tumor without worrying about not having adequate tissue for testing multiple genes. A liquid biopsy can reveal driver mutations, diagnoses, recurrence, resistance mechanisms, treatment response, and prognosticate outcomes. The primary use for liquid biopsy, however, is to detect actionable mutations. For patients with lung cancer, liquid biopsies can detectEGFRmutations.2

Results from the NILE study, a head-to-head trial in which genomic testing was performed upon 282 newly diagnosed patients with advanced NSCLC, showed that liquid biopsy is, in fact, a viable alternative to tissue genotyping. In some areas, like limiting the time (from 15 days to 9 days) and use of resources for clinical evaluation, the trial showed that blood-based testing might be preferable compared with tissue-based testing.

Among the 282 patients, a guideline-recommended biomarker was found in 77 patients with cell-free DNA testing compared to in 60 patients with standard tissue genotyping (27.3% vs 21.3%;P<.0001 for non-inferiority). Cell-free DNA testing showed a clinical sensitivity rate of 80% for identifying any guideline-recommended biomarker in tissue-positive patients. Concordance was more than 98.2% for all FDA-approved targets in lung cancer with a 100% positive predictive value for cell-free DNA testing compared with tissue testing.

In an interview withTargeted Oncology, Mark Socinski, MD, executive medical director of the AdventHealth Cancer Institute in Orlando, Florida, spoke about the use of liquid biopsies in lung cancer evaluation and management, as well as key takeaways and limitations from the NILE study.

TARGETED ONCOLOGY:What is the current role of liquid biopsies in lung cancer?

Socinski:Liquid biopsies are an integral part of the evaluation and management of patients. We know that tumors release cell-free DNA. It can be detected in the plasma. Techniques exist to interrogate that resource and you can diagnose oncogenic drivers with blood-based testing [and] perhaps even have an advantage over tissue-based testing. The blood-based [testing] tends to be easier. It's a simple blood draw. The results get to you much quicker than tissue-based testing and the sensitivity of the assay is quite good. There is a little bit of concern about false negative results, so, a negative blood result cannot be taken as gospel. In my practice, I do blood-based testing along with tissue-based testing in all my advanced patients with non—small cell lung cancer.

TARGETED ONCOLOGY:Could you discuss the NILE trial? What were the key takeaways?

Socinski:The NILE Trial is an interesting trial [which] let oncologists who were seeing patients with lung cancer work up the patient from a molecular point of view. [This included things like] tissue-based biopsies [and] getting the testing done. What they did with these 282 patients is add Guardant360 on top of the standard work up or [add] blood-based testing. What they showed actually is that the plasma-based testing detected more actionable findings than the tissue did. It kind of exposed the limitations we have with tissue. [Those limitations are] not getting enough tissue to test [and] having the tissue be exhausted by doing multiple tests on it. So, I think it was a really nice study showing the clinical usefulness of plasma-based testing relative to the difficulties of tissue-based testing. We've always historically felt tissue was the gold standard, but I don't think it is. I think it's a gold standard not the gold standard. And I would add that the gold standard, in my opinion, really is tissue and blood.

TARGETED ONCOLOGY:Were there any limitations to this research?

Socinski:The limitations were more so for the tissue aspect of it than the plasma aspect of it. However, we do have to realize that you get false negatives in the blood based upon occurrences [like] less shedding of tumor DNA. So, you have to realize that you will find things in tissue that you won&rsquo;t find in blood. But, actually, the opposite is also true. You will find things in blood that you don't find in tissue. It gets back to my previous comment about these being complementary. Again, I think the best thing an oncologist can do for a patient with lung cancer is to diagnose an oncogenic driver because that opens up the possibility of targeted therapy. We know that if you have an identifiable target, in many cases likeEGFR,ALK,ROS1, we have specific targeted agents that are much more highly effective than chemotherapy, immunotherapy, [and] other options for these patients. So, you really want to find these patients. I think the strategy should be to leave no man behind and leave no stone unturned and to do all the testing that you need to do to try to find these patients.


  1. Leighl NB, Page RD, Raymond VM, et al. Clinical utility of comprehensive cell-free DNA analysis to identify genomic biomarkers in patients with newly diagnosed metastatic non-small cell lung cancer [published online April 15, 2019].Clin Cancer Res. doi: 10.1158/1078-0432.CCR-19-0624.
  2. Ou SI, Nagasaka M, Zhu VW. Liquid biopsy to identify genomic alterations.Am Soc Clin Oncol Educ Book. 2018;38:978-997. doi: 10.1200/EDBK_199765.
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