Optimizing Biomarker Testing to Guide Early-Stage NSCLC Treatment: Robert Kratzke, MD

In part 1 of a recent interview, Robert Kratzke, MD, professor of medicine at the University of Minnesota, discussed with The American Journal of Managed Care^® (AJMC^®) which biomarkers clinicians should consider essential when developing a treatment plan for early-stage non–small cell lung cancer (NSCLC), how to evaluate next-generation sequencing (NGS) panels, and what to do when testing does not identify an actionable alteration.

Kratzke's comments build on insights shared during the panel discussion, “Precision in Practice: Implementing Biomarker Testing in Lung Cancer,” at the Minneapolis Regional Institute for Value-Based Medicine® event on June 23, 2026.

This transcript has been lightly edited for clarity.

AJMC: Biomarker-driven therapy has moved into earlier-stage lung cancer over the past few years. When developing a treatment plan, which biomarkers do you consider essential to test for, and which are more "nice to have"?

Kratzke: Well, certainly the 2 essential ones are EGFR and ALK, because there are FDA-approved therapies for patients with even early-stage cancer. After the recent presentation at the 2026 annual meeting of the American Society of Clinical Oncology in the plenary session regarding selpercatinib. I'm confident that any day now we'll see approval for RET inhibitors in the early setting.

I think many of us feel that other actionable mutations should be looked at. There was some discussion at the IVBM meeting about, for example, ROS1. The studies are currently ongoing, but many of us feel that it would be reasonable to talk to a patient about targeted treatment with an early-stage lung cancer. But to answer your question, the ones that are absolutely necessary are EGFR, ALK, and RET

AJMC: With so many NGS panels available, what should clinicians look for to ensure they are obtaining the information needed to guide treatment decisions?

Kratzke: I think it's critical to obviously include all the actionable markers, which I almost lose count of, but I think there are 11 or 12 of them by now. I think most of us would like to continue to see widespread reporting of markers such as STK11 and KEAP. I think increasingly those will play a role in shaping our treatment choices, particularly maybe with immunotherapy.

So, a broad-based panel is really almost necessary, in my opinion. What do I mean? I mean, commercial vendors will offer 3, 4, 5 gene panels, but most of us would frankly like to see a minimum of a 500 gene panel. I think most of the major vendors are doing that now. Certainly, we do that at the University of Minnesota in-house. So, a broad-based NGS panel, which most of them are, is what I definitely look for and require.

AJMC: If testing does not identify a biomarker linked to an FDA-approved therapy, what are the next steps? What treatment options or clinical trial pathways do you consider for these patients?

Kratzke: Certainly, clinical trials are always at the top of our mind. We have, locally, trials for stage 4 patients that are not only business and industry but investigator-initiated here at the University of Minnesota. Frankly, to go on most of those trials in the stage 4 setting, your tumor has to not possess 1 of the actual biomarkers that we were talking about, like EGFR or ALK.

We haven't mentioned PDL1, which people could say is a biomarker. Usually, when we talk about biomarkers in this context, we're talking about genomic ones, but certainly one of the first things I'm looking at is PDL1. If it's greater than 50%, most of us, I think, around the country who are lung cancer specialists would consider immunotherapy alone. If it's a lower-expressing or negative one, we would consider chemotherapy and immunotherapy. So, if the genomic biomarker comes back negative, we certainly are looking immediately at PDL1 status, which is an immunohistochemistry step.

But as you pointed out, we would always be looking for clinical trials. Most centers have a current array of trials available to them, but if they don't, it can be difficult if you're not part of a group to cast a wide net and look where other trials are. Frankly, most patients, even if they're facing a deadly cancer, are not willing to travel 500 miles for a clinical trial. So, you could look locally.

Here in Minnesota, we're just launching a Minnesota Connect, or MNconnect, thing that will allow practitioners on the website to look at all the clinical trials in a given disease, like lung cancer, available in the state of Minnesota. So, that's a nice thing that we have.