Unmet Needs and Role of Immunotherapy in Stage 3 NSCLC

D. Ross Camidge, MD, PhD:The real challenge with stage 3 non—small cell lung cancer is despite our best efforts, the cure rate is low, somewhere between 15% to 25% depending on where you get your data. That means that the vast majority of people are going to relapse. Now some of that is because there’s a failure locally, but much more commonly it’s because there’s distant metastatic disease that you didn’t know would then manifest later. And so, the risk that there’s hidden metastatic disease is very high.

Immunotherapy—in particular we’re talking about monotherapy with either a PD-1 or a PD-L1 inhibitors—has revolutionized the care for certain subgroups of non—small cell lung cancer in recent years. We don’t entirely know who it works in. But there are dramatic responses maybe in about 20% of an unselected population. And if you respond, your duration of response is very long, and that almost certainly is the major group driving the PFS and overall survival benefit. However, there are probably survivors who benefit from this who aren’t manifesting responses.

Now what we’ve seen is we can enrich that population that is deriving benefit from immunotherapy by certain biomarkers. PD-L1 expression is one that is a continuous variable. Higher levels are associated with more benefit, most recently tumor mutation burden, which is, again, a continuous variable measured in different ways that you can enrich for those who derive benefit.

Now people asked, “Well, hey, if you’re getting your immune system to be active, what about using this in an earlier staged disease?” Maybe those hidden metastatic bits, which are just sitting there asleep, maybe that you could actually change the cure rate in the same way that a very low volume of disease chemotherapy can actually change the cure rate in the adjuvant setting. So, that’s where the role came about of adding it in to a stage 3 study. There’s also a theoretical benefit—and I emphasize theoretical benefit—that radiation somehow releases more antigens, makes these things more immunogenic, although I would say that is hard to prove in the real world.

Transcript edited for clarity.