Dr Dietrich Transcript

Biomarker testing in lung cancer has been an integral part of establishing a diagnosis. It’s truly been an addition that has not only changed the way we prognosticate lung cancer, but also the way we approach different molecular and immunophenotypic subtypes of lung cancer. So it has truly become part of the diagnosis of metastatic and locally advanced lung cancer in the last couple of years, and certainly part of any initial workup for metastatic lung cancer in this setting.

The initial biomarker testing for non-small cell lung cancer should encompass at the very least the FDA-approved markers of PD-L1, EGFR, ALK, BRAF and ROS1. I think there are a number of other mutations and features that should be tested for that are not very common, but that are certainly changing the outcome of individual patients. Those include the amplifications and exon 14 skipping mutations in the MET gene, RET mutations and translocations, microsatellite instability and mismatch repair deficiency, which is not very common, but certainly still occurs in non-small cell lung cancer.

The addition of PD-L1 and, in the future, additional markers for immunotherapy, predictive value, at the very least, of the five of BRAF, EGFR, ALK, ROS1 and PD-L1, are the absolute minimum for characterization of non-small cell lung cancer in the beginning. Additional ones in broader panels should be added if enough tissue is available and the test is feasible in the clinical setting.

Concerns exist for biomarker testing and delayed initiation of therapy. I think it is most important to understand biomarker testing as part of the diagnostic characterization of a disease. Therefore, the delay that you would see with next-generation sequencing is part of the process. Typically, we aim at 10 days or less for biomarker characterization, which requires a more streamlined process. It’s kind of an institutional effort to obtain tissue and bring it to biomarker testing relatively quickly, hopefully in parallel to the immunohistochemical workup for characterization of the histology.

Another modality that can be exceedingly helpful in this setting is the addition of liquid biopsies. These have been found to be tremendously helpful in adding the genetic information to an initial workup. And if you find a mutation that is actionable plus an analysis on the immunohistochemical level, you can actually start your treatment within 1 to 1 week to 10 days on most reliable.

Beyond the FDA-approved biomarkers that are currently part of the standard panel for non-small cell lung cancer workup, there are a number of additional biomarkers that are exceedingly helpful to change an individual’s patient outcome in the disease setting. Those include the RET translocation and mutations. I think we have seen some wonderful data at ASCO, both establishing the feasibility and specificity for these drugs and establishing RET as a very interesting target. I think we’ll be seeing the arrival of NTRK inhibitors in the next couple of months that will be helpful. But I think there will be a number of others that transcend through the histologies that will become part of the routine panels, and as next-generation sequencing becomes the standard of care, width of investigation is virtually unlimited, and will include even the rarest biomarkers for us. But I think during the next couple of months, I think NTRK, RET and probably additional markers for immunohistochemistry for immunotherapy prediction will be part of the armamentarium of our non-small cell lung cancer workup.

Biomarker testing is one of the truly grand challenges of biomarker development and biomarker testing in non-small cell lung cancer. It basically starts its very first step at the radiographic analysis of a potential or suspected cancer, and then an early discussion between oncology and the interventionalist, whether it’s the interventional radiologist, the thoracic surgeon, a GI interventionalist or another subspecialist that would be available for the procurement of tissue.

It’s important to understand what the tissue requirements are. It’s no longer sufficient to establish a histological diagnosis for us. The FNA-guided tissue procurements are typically insufficient for meaningful biomarker testing, and basically leave an insufficient diagnosis.

I think that is a disease education that has to transcend through all layers. Sometimes difficult to do when you have referrals from multiple sources or from outside institutions. But it has to be the common standard, and enough tissue is obtained so that we can basically perform all the testing need to give proper characterization on the molecular level for a non-small cell lung cancer. This entails typically a core needle biopsy or sometimes even an excision that will help us to get enough tissue to, in the end, reliably produce a result that will help us choose the first, best treatments then for patients initially.

Between academic and community practices, I believe the differences frequently lie in the multidisciplinary approach to a patient. When it comes to biomarker setting, I think a lot of the community practices have been very forthcoming in adopting next-generation sequencing. However, if you are not working in a multidisciplinary setting where you have immediate access to your colleagues in surgery and interventional radiology and other subspecialties, it may be difficult to have a reliable outcome and to avoid delays that occur from having tissue in outside laboratories from having insufficient tissue amounts obtained or for tissue being used up for immunohistochemical analyses that may not be as important in 2018 as they may have been 20 years ago.

So I think the multidisciplinary approach, whether it occurs in academia or in the community setting, is highly important for proper immunohistochemical and molecular characterization of disease.  And I think there is a benefit to streamlining these cancer teams into a very well-communicated network.

On the other hand, the adoption of next-generation sequencing, I believe, has had a tremendous uptick in the community setting with recent FDA approvals for two of the next-generation sequencing panels. I believe we’ll see that this will penetrate into the market further as more diagnostic and therapeutic options become available for patients in all settings for cancer treatment.