Jeffrey Melson Clarke, MD, discusses the latest developments with biomarkers in NSCLC.
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.Clarke: 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. 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. 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.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. 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. With genotyping, if we do see EGFR or ALK 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, and ROS1 alterations, as well as others that are potentially actionable and can result in good therapeutic options for patients.
On the immuno-oncology side, if we see a high PD-L1 score using the PD-L1 IHC 22C3 pharmDx assay than using pembrolizumab (Keytruda) in those patients is indicated in the frontline setting. One of the most exciting and emerging biomarkers today is tumor mutational burden (TMB). We have known for several years that TMB can predict response and benefit from immunotherapy. There is a growing amount of evidence showing that it is relevant in lung cancer and we will be looking to the future to prioritize therapeutic options for patients based on TMB. On the targeted therapy side, everyone is excited about the results of the FLAURA study with osimertinib in the frontline setting for EGFR-positive patients. There seems to be a meaningful improvement in progression-free survival over the standard targeted therapies. That is a recent and exciting result.
We are also going to be looking towards the results that should be announced soon from the frontline chemotherapy and pembrolizumab study, as well. We have had a recent announcement that the combination of immunotherapy with nivolumab (Opdivo) and ipilimumab (Yervoy) should benefit patients who had a high TMB. Those are some exciting upcoming results that we will be looking at.