Jeffrey Melson Clarke, MD
Biomarkers have revolutionized the treatment of patients with non–small cell lung cancer (NSCLC), becoming an essential component of treatment and enabling the implementation of precision medicine.
“The biggest point about biomarkers is that patients should be tested and the treating physicians should be actively considering and thinking about the biomarkers that are relevant for that patient,” said Jeffrey Melson Clarke, MD. “Physicians need to be incorporating testing into routine practice, both with genotyping and using PD-L1 status.”
Clarke notes, however, that the development of new biomarkers is critical to further enhancing precision medicine in NSCLC.
In an interview during the 2018 OncLive®
State of the Science Summit™ on Non–Small Cell Lung Cancer, Clarke, an assistant professor of medicine in the Department of Medicine at Duke University School of Medicine, discussed the latest developments with biomarkers in NSCLC.
OncLive: Please provide an overview of your presentation on biomarker testing for patients with NSCLC.
: The use of biomarkers for NSCLC is incredibly important. We have seen biomarkers evolve over the past several years for routine clinical use to directly care for patients with NSCLC. Typically, biomarkers for NSCLC can be broken down into genotyping and determine selection of patients for immunotherapy. There are different ways to perform genotyping for patients with lung cancer, either using tissue-based genotyping methods or plasma-based methods.
On the immuno-oncology side, PD-L1–expression measurement remains the most well-validated and widely used biomarker that we have.
Would you say that PD-L1 is reliable as a biomarker?
PD-L1 is a dynamic and heterogeneous biomarker that can certainly be somewhat problematic. For example, patients can have high expression and not respond to immunotherapy or have low expression and still derive benefit from immunotherapy. It is an imperfect biomarker.
You mentioned the different methods of testing, either plasma-based or tissue-based. What is latest with liquid biopsies in the field?
Liquid biopsies can be useful in our patient population to potentially spare them from additional biopsy procedures that can incur a nontrivial risk when the lung is biopsied. Liquid biopsies can be very helpful in detecting EGFR
alterations or other actionable mutations in our patient population.
The drawback to their use is their sensitivity is moderately high, although not perfect. The important take-home point is that if you have a negative result with liquid biopsies, it is still potentially important to consider testing tissue directly.
Is it easier to detect some biomarkers than others?
We have the most data around testing for EGFR,
but it certainly can be used to test other actionable alterations that we see commonly in our patient population.
How heavily do physicians rely on biomarkers to determine a patient’s course of treatment?
The use of biomarkers in our patient population is important, particularly in nonsquamous histology where genotyping can dramatically change what types of therapies are offered and the targeted therapies that can be used. Certainly, with immunotherapy as well, having PD-L1 expression as a result can be very helpful when dictating therapeutic options for patients.
Can you speak to different biomarkers and what courses of treatment they are associated with?
With genotyping, if we do see EGFR
alterations, then pursuing targeted therapies around those alterations is appropriate by using EGFR or ALK inhibitors. There are a number of other actionable alterations that we look for as well, including HER2, MET, RET,
alterations, as well as others that are potentially actionable and can result in good therapeutic options for patients.