Future Role of Immunotherapy in NSCLC

Paul K. Paik, MD:Immunotherapy given in patients who are newly diagnosed and untreated really has been a boon for our patients, again by-and-large because of the very good efficacy data from KEYNOTE-024 with treatment with pembrolizumab. It is not only more effective, but we know also from the data that it is, in general, much better tolerated. The rate of ≥3 adverse events for immunotherapy in general compared with chemotherapy is one-third of what we end up seeing. And so, overall, the side effects that are perhaps most meaningful to patients—nausea, vomiting, hair loss, decreases in blood cell counts that lead to infection—these things generally don’t happen with immunotherapy. It is important to note, of course, that there is a subset of toxicities that are unique and idiosyncratic to this group of treatments, which are the autoimmune diseases essentially that emerge. But even here, the rate of ≥3 adverse events is relatively low for single-agent immunotherapy, at around 7%.

With all of the activity in the frontline space—and arguably, this is the most important space for us to identify the best treatment option—these are our patients who generally present in, for many of them, the best condition that they’re ever going to be in. And we know, in terms of selecting the right treatment for patients, the best treatment option has the best and biggest potential impact for the quality of life and the survival of our patients. With all of the activity that’s there that’s happening very quickly in competing trials with competing biomarkers, we, as a field, are going to have to sit down and very carefully go through all of the data to really help to identify in whom one regimen should be given over another. This will have to do with thinking about which biomarker is being looked at. PD-L1 expression or tumor mutation burden are the two that have emerged now.

The latter, fairly quickly, has something that’s going to be important to consider. The performance status of the patient, preexisting diseases, whether or not they would be able to tolerate combination therapies, all of these things are things that we’re going to have to consider all at once when we’re making decisions for our patients. This is going to be, as a result, a much harder job until we get all of the requisite data in place. So, what I would recommend for our oncology colleagues out there is to keep a very careful eye out on things, to really take a measured approach to all of the data that are coming out, and to really not have a kneejerk reaction in terms of prescribing one regimen over the other. We really are going to have a wide selection, as we actually do now, of different options to end up picking. And so, we really do carefully consider how we’re going to end up doing this, and hopefully we’ll to be able to assist with this as time goes on.

Transcript edited for clarity.