Current use of the Tumor Mutational Burden Biomarker to Guide Treatment Decisions in Adults with Advanced Metastatic Non-Small Cell Lung Cancer – A Retrospective Observational Study
Abstract Background: Immunotherapy has become first-line in metastatic non-small cell lung cancer (NSCLC). Biomarkers are used to help identify individual patients for potential response to certain therapies. Tumor Mutational Burden is a biomarker that has been demonstrated to predict a durable response to these agents. Although the National Comprehensive Cancer Network guidelines were just updated to mention tumor mutational burden in 2018, tumor mutational burden testing has been performed clinically for some time. How clinicians have been using tumor mutational burden results remains unclear. This study aims to describe the use of tumor mutational burden, and related treatment decisions, in a clinical setting for patients with metastatic NSCLC. Methods: This is a descriptive, observational study that retrospectively followed a cohort of 130 patients with metastatic NSCLC, treated at Huntsman Cancer Institute in Salt Lake City, Utah, who have undergone comprehensive genomic profiling, have tumor mutational burden reported in the electronic medical record, and have received therapy of any type for NSCLC. Four reviewers examined electronic medical records to identify desired values from each individual chart. Patients were separated into three groups based on tumor mutational burden results: high (greater than 20 Mutations/Megabyte) intermediate (10-19 Mutations/Megabyte), and low (less than 10 Mutations/Megabyte). Patients were followed to identify what first-line and second-line therapies were received against their TMB levels. Using Microsoft Excel, data were summarized into medians and groups were compared based on therapy received. The results are discussed based on identified vs. expected trends. Results: A total of 130 patients met the inclusion criteria. There were 52 patients who had TMB results before first-line therapy. Immunotherapy was chosen as first-line treatment in a greater percentage of patients in both the low and intermediate TMB groups, 60% and 53% respectively. In the high TMB group, 44% were treated with immunotherapy as first-line. The median time from diagnosis to TMB testing was 41 days. The median turnaround time from requesting a TMB test to obtaining results was 13 days. Conclusion: These results suggest that TMB, between 2012 and 2019, was not used in any obvious pattern to guide treatment choice in this population. It is unclear why this is the case, but it is likely that providers were not yet comfortable with the clinical utility or reliability of TMB. We expect this to change as TMB increases in popularity as more data and guidance for its use becomes available.
This was clear enough that I a layman could understand. Thank you.
I am glad that it was clear and easy to understand. Thank you for looking at my poster and for your comment.
Jason, nicely done! It is so nice to see the studies come to fruition. While I appreciate the limitations, I thought you did a good job highlighting the significance of your findings. I was surprised with the IMT was used more in the lower TMB status patients, but I wonder if you’re correct in that the higher TMB burden patients might have more contraindications for the IMT. It will be interesting to see moving forward whether this is the case or whether there will just be increased adoption of TMB as a biomarker in the future.
Dr. Keefe, It was very interesting and unexpected that IMT was used in lower TMB status patients! I think it has to do with the uncertainty surrounding TMB and the comfort that practitioners likely have with using the current gold standard assay, which is PD-L1 expression. I think we will see a shift towards TMB as the body of evidence grows for this new biomarker. Thank you for looking at my poster and for your feedback.
Nice job, Jason! You organized your data succinctly and summarized your findings really well. I think this will be an interesting area for future studies.
I appreciate your feedback Angie! Thank you for looking at my poster and for your comment!
Great job Jason. Maybe as we develop more selective therapeutics for NSCLC the mutational information will have more impact on therapy choices
Good job Jason! It was great to see the results of your study after following it this past year of the various drafts we had. It will be interesting to see how TMB will be used in the future.
Nice job on your poster. Looks like alot of research went into your presentation. Way to go. Sure exited you’ll be finishing up soon!
Good job on this Jason! Came out well in the end, despite rush to get results. Diana
Jason, your poster is well-written. You have conveyed a lot of information in easy to read format.
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