Case 4: Treating Stage IV NSCLC With Novel Approaches



Benjamin P. Levy, MD:So now we’ve got 3 trials that have given some answers. Some haven’t. We’ve got KEYNOTE-189, we’ve got IMpower150 of the 4-drug regimen, and then we’ve got dual-checkpoint blockade for high TMB [tumor mutation burden], which didn’t shake out in terms of overall survival. Sam, do you do TMB at all on your patients? Are you being asked to do tumor mutation burden in non—small cell lung cancer?

Samuel Caughron, MD:We do get asked about TMB and get asked to do TMB in some patients. I think 1 of the challenges right now for TMB is there’s not consensus about how it should be performed. And so within the diagnostic community you certainly need to do next-generation sequencing. There’s a question about how many megabases you have to sequence to actually get an adequate power to the value you come back with. There is also the question of, do you have to have a normal match to get an accurate TMB? There’s no standard out there right now for how TMB is done. I think that’s muddied the waters, in terms of being able to accurately determine how TMB is useful in patient care. We get it. I’ll do it, if it’s required. But in general, I think you have to be careful. Just because you have a number, knowing how good the data are behind that number is important.

Benjamin P. Levy, MD:Yeah, good point. Are you using dual-checkpoint blockades in your non—small cell lung cancer patients? Are you using IMpower150? Have any of these regimens made their way into your clinic, routinely?

Lonny Brett Yarmus, DO:I think, Ben, you so nicely highlighted the treatment algorithm, and the options that we have for our patient presented in this case. I think the main goal is to find the perfect patient for each treatment option. Perhaps someone who is extremely symptomatic and may be poorly differentiated, as we were discussing before, may be a good candidate for the quadruplet regimen, as opposed to someone for whom you have the luxury of having TMB on. And perhaps it is like this patient at TMB of 18 megabases, or very high tumor mutation burden, over 10 megabases. This might be someone for whom if you have this information up front, it may be worth a discussion regarding up-front nivolumab-ipilimumab versus KEYNOTE-189 versus the quadruplet regimen.

Benjamin P. Levy, MD:I think we’re still waiting for the nivolumab-ipilimumab data to be a bit more formalized and mature to make those decisions. We’re not routinely. Johns Hopkins [Sidney Kimmel Comprehensive Cancer Center] does a TMB on all our patients. It drives me crazy because it does sum up a lot of tissue. But we are an immunotherapy institution and we do TMB, and I think there may be some value to it in the future. But in routine clinical care, I don’t think we’re there yet. I’m giving it a hard time. I’m glad we’re doing it because I think it can be used in the future.

This has been a wonderful discussion. Thanks, everyone, for your insight and your ability to kind of layer in your unique perspective to these cases. Dr Jain, thank you. Dr Yarmus, Dr Caughron, Dr Walker, and Dr Preeshagul, you’ve all done a wonderful job layering insights in these thoughtful case presentations and this lively informative discussion.

To our viewing audience, thank you for joining us for thisTargeted Oncology™ Virtual Tumor Boardpresentation. We hope today’s discussion was a valuable use of your time and that you acquired some practice knowledge that you can take back to your clinic today.

Transcript edited for clarity.

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