Navigating Biomarker Testing in Early-Stage NSCLC: Robert Kratzke, MD

Robert Kratzke, MD, professor of medicine at the University of Minnesota, discussed with The American Journal of Managed Care^® 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 points he made 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.

He identified EGFR and ALK as the 2 essential biomarkers to test for in early-stage disease since both already have FDA-approved targeted therapies available for these patients. Kratzke added that RET should now be considered essential as well, citing data on selpercatinib (Retevmo; Eli Lilly and Company) presented during the plenary session at the 2026 American Society of Clinical Oncology Annual Meeting, which he expects will lead to the imminent approval of RET inhibitors in the early-stage setting.

Beyond those 3 biomarkers, he highlighted growing interest in other actionable alterations, including ROS1. Although studies are ongoing, Kratzke said many clinicians already believe it is reasonable to discuss targeted treatment with early-stage patients whose tumors harbor these mutations.

Regarding NGS panel selection, he recommended broad-based panels that assess at least 500 genes rather than smaller commercial panels that cover only 3 to 5 genes. Kratzke noted that most major vendors, as well as the University of Minnesota's in-house testing, already meet that standard. Therefore, he emphasized that broad panels should capture all currently actionable biomarkers, now totaling roughly 11 or 12, as well as emerging markers such as STK11 and KEAP1, which he expects will play an increasingly important role in treatment selection, particularly for immunotherapy.

Kratzke also flagged the importance of PD-L1 testing, noting that it is one of the first results he reviews. PD-L1 expression of 50% or higher generally supports immunotherapy alone, whereas lower or negative expression typically favors a chemotherapy-immunotherapy combination.

When genomic testing fails to identify an FDA-approved actionable alteration, Kratzke said the immediate next step is to review PD-L1 status by immunohistochemistry to guide treatment selection while also considering clinical trial enrollment. He noted that eligibility for many trials in the stage 4 setting requires patients to lack actionable biomarkers such as EGFR or ALK.

For practices without a robust clinical trial portfolio, Kratzke encouraged clinicians to broaden their search while recognizing that many patients are unwilling to travel long distances to participate. He concluded by highlighting Minnesota Connect, Minnesota’s newly launched platform that allows clinicians to search for clinical trials across the state, as an example of how regional resources can help connect patients with nearby research opportunities.

“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,” he said. “So, that's kind of a nice thing that we have.”