Practice Changing Trials in Advanced Non-Small Cell Lung Cancer - Episode 10

Biomarkers for Selection of Immuno-Oncology Agents in NSCLC


Benjamin P. Levy, MD: Let’s wrap up this session, and I’ll ask you all to get out your crystal ball for I-O therapy and forecast where we’re heading with this. And Naiyer’s kind of already alluded to this. Are we OK accepting that immunotherapy may be given up front to all patients irrespective of a biomarker and maybe concentrating on the science in the refractory setting for biomarkers? Or are we more inclined to continue to search for better biomarkers up front? Where is this going? Hossein?

Hossein Borghaei, DO, MS: Look, I think the paradigm that we’ve been operating on, you look at the NCI, look at ASCO, look at all the guidelines, what is it that we always emphasize? Personalize your delivery of care, heterogeneous disease. You want to be able to identify the right patient for the right treatment. And this hodgepodge of doing everything up front just because we have a couple of data—it’s something that’s not going to be effective for most of our patients.

We want to deliver care to the appropriate person so that if there are toxicities, it’s justified; so if there are responses, patients could really benefit from it. So, going back to what Naiyer was suggesting, high TMB, high PD-L1, the data right now say to use I-O. Remember that in this country, we have data that up to 30% of non—small cell lung cancer patients never make it to second-line therapy. In the older data set, platinum doublet only, I understand. But nonetheless, we have that in the back of our head.

So, you want to give the appropriate care up front. If the paradigm right now says PD-L1 and TMB is what we have to choose, then that’s what we use. And we offer I-O up front. And then for the ones that are lower expression, maybe a combination with chemotherapy; for the ones that have no expression, maybe chemotherapy alone until we learn. But your comment that we need the science behind it is absolutely right, and I think that’s the part that’s lagging and that’s the part that always lags and gets us into these kinds of binds that we are in right now. So, the science has to progress a little bit faster.

Suresh S. Ramalingam, MD: And I think this clearly is a need for further refinement of biomarkers. We’ve talked a lot about exciting efficacy in these patients. What we haven’t talked much about is the minority of unfortunate patients who end up with significant toxicities, and that can be crippling for some patients. So, there is an ugly side to immune checkpoint inhibition, and that should prompt all of us to go to the drawing board and continue to look for markers so we precisely select patients who should get these therapies.

Benjamin P. Levy, MD: What were your thoughts on this? You’ve been intimately involved in a lot of the research efforts. Do we need better refinement? You’re OK with the up-front therapy in a select group of patients?

Roy S. Herbst, MD, PhD: Well, we’re starting at such a higher level than we had before, so it really is amazing, and it’s good news for patients. That said, there’s no doubt that we have to personalize this, as we’ve heard, and it’s not going to be effective in everyone in the frontline setting. Studies are now being done in exceptional responders, those 4-, 5-, or 6-year patients. What is it about them? Many others might need other things. They might need combinations, either combinations of immunotherapy. I wouldn’t have thought it, but I think that chemotherapy does have a role, and with the antiangiogenic, it’s really going to be understanding the patient’s tumor and their immune system. So, both.

And then personalizing that care and thinking that we spent 15 to 20 years figuring out how to do this with targeted therapy, but we’re only in the infancy of immunotherapy. So, we shouldn’t think that it would work in everyone. But I bet by the time we’re doing this 5 years from now, we’ll know who should get immunotherapy up front, who should get a combination, or who maybe should not get it until the later stages of a disease.

Transcript Edited for Clarity