Practical Application of Recent Clinical Data for Immunotherapy in NSCLC - Episode 5

TMB as a Predictive Biomarker in NSCLC


Leora Horn, MD, MSc, FRCPC: You brought up tumor mutation burden [TMB]. CheckMate-227 looked at nivolumab with or without ipilimumab. It was a very complicated study. There were almost 2000 patients. We’ve slowly seen data come out, 1 bite at a time. How are you using tumor mutation burden right now? What are your thoughts on what’s being presented with CheckMate-227? Is it a regimen that you’re using or are excited to use in your patients with metastatic disease?

Edward B. Garon, MD: So far, we have not routinely incorporated tumor mutation burden. One issue we have is that our institutional panel for mutations looks at 10 mutations or gene abnormalities, including the 4 genomic abnormalities for which there are associated therapies. With a panel like that, we internally do not get the data that’s needed for tumor mutation burden. This will be an issue, particularly if we are in a situation where it becomes clear that this data is going to be practice-changing.

I think there is certainly reason for enthusiasm. I think that tumor mutation burden clearly predicts whether patients will have progression-free survival. We’re still awaiting overall survival data. If that comes back positive, I think we are going to have to make some significant changes, in terms of how we deal with the pathology specimens. Is a 10-gene panel internally going to be sufficient if we have a group of patients who basically have a therapy that is driven by that, which will dictate their care?

I think there are still some questions, and I share some of the concerns you bring up in your question. The data has come out a little bit at a time. This is concerning. This is a very large study. Often, the data shown is based on a very small subset of that. I do look forward to getting a robust data set where we can really evaluate the data in its totality. What is the added benefit of the ipilimumab, for instance? This is still a very interesting question. It is one that I still find hard to answer with the data that’s available to me.

Leora Horn, MD, MSc, FRCPC: Do you have access to TMB? At our institution, we do not. We also have a small 40-gene panel that comes back within a few days. What are you guys doing?

Thomas E. Stinchcombe, MD: We have the same problem. The gene panel is like 40 or 50 genes, and I think the challenge is that it doesn’t encompass all of the targets that we want in the modern lung cancer world. And, we don’t get the TMB. I would say that I’m starting to see more patients with Foundation Medicine testing, which was used in the study. We’re starting to send more out to that for testing, just to try and get the TMB. I’ve not implemented nivolumab/ipilimumab based on the data, and I would caution against it until we really see the overall survival benefit and updated toxicity in regard to that combination.

Transcript Edited for Clarity