The Changing Immunotherapy Landscape in Lung Cancer

Transcript:Anne S. Tsao, MD: Immunotherapy has taken the whole solid-tumor drug setting by storm, and lung cancer is a perfect example of that. For patients who have high PD-L1 expression—over 50% in the frontline setting—we would give an immunotherapy frontline. In patients who don’t have that expression at such high levels, they can get systemic chemotherapy upfront and then consider getting an immunotherapy second-line. Now, you have your choice in the second-line setting of atezolizumab, nivolumab, or pembrolizumab, although pembrolizumab is the only agent in the second-line setting that does require you to have PD-L1 IHC expression.

David Spigel, MD: We’re trying to understand if our patients are candidates for immunotherapy in the first-line setting, and so we ask for PD-L1 expression results on all newly diagnosed patients. Sometimes, however, you don’t have enough tissue to do that. You’re asking for a lot of things—molecular testing and PD-L1 testing—and sometimes you just don’t have enough tissue to get that. Here, you have a patient whom you want to give immunotherapy to, but, for right now, we have to define the PD-L1 expression at a high enough level to justify giving pembrolizumab.

What do you do in those situations? Well, sometimes you can re-biopsy, but I have to be honest, that doesn’t happen very often—at least in my center. In that situation, where we’re really wanting to get started with therapy, a re-biopsy is very important, and we do a ton of them. But in that scenario, where you’re meeting somebody and you’re ready to get started with therapy, sending them in for a re-biopsy and PD-L1 testing again can sometimes take a couple of weeks to get done. There are patients who can wait to do that.

There are also folks where you’ll just start with chemotherapy, understanding that immunotherapy could be a second-line option for them. I always believe that giving the best therapy first makes the most sense, and I’ve had patients where we’ve started with chemotherapy and later gotten back PD-L1 testing, where I transition patients back over to pembrolizumab after they started 1 cycle of chemotherapy. I think that happens to some extent, but it’s not very common. I think most doctors are going to stick with whatever they start with, and when that is exhausted, they’ll move on to something else.

It’s important to mention that in the later-line settings—second and beyond—the use of immunotherapy is not restricted by PD-L1 expression testing. So, you can give at least a couple of these agents right now, atezolizumab and nivolumab, without having to have PD-L1 expression by any measure to justify using those drugs. Immunotherapy can be a part of anyone’s therapy, but that expression level will determine whether it gets to be in the first-line treatment or it gets to be used in a later line of care.

There’s a lot of excitement about immunotherapy’s role in lung cancer treatment, and right now we have single agents that are available in the first-line and later lines of care for both squamous and nonsquamous patients. We are waiting on the results of some pivotal trials that are going to tell us whether chemotherapy with immunotherapy or immunotherapy combinations without chemotherapy could be important new standards of care. The checkpoint inhibitor class involves both PD-1 and PD-L1 agents, and we have drugs from each class that are approved right now.

We have other checkpoint inhibitors, and right now, those are CTLA-4 antibodies. In lung cancer, there’s not an approved CTLA-4 antibody, but there are at least 2 major efforts under way combining a PD-1 inhibitor with a CTLA-4 antibody or a PD-L1 inhibitor with a CTLA-4 antibody. Large registrational first-line studies are in progress. They’re fully enrolled. We’re just waiting on those results to see if these immunotherapy doublets are better than chemotherapy in the first-line setting. And then, even more so, there are these therapies that PD-L1 testing is going to be necessary in to determine whether they work well or not or if you can use these drugs without PD-L1 expression testing. So, a lot is still to come, but these results are not far away. We’ll have these answers pretty soon.

Transcript Edited for Clarity