The Case for Using Immunotherapy for Patients With Low or Negative PD-L1

At the Great Debates & Updates in Lung Cancer meeting in New York, New York, Hossein Borghaei, DO, MS, Fox Chase Cancer Center, Philadelphia, Pennsylviania, debated in favor of using immunotherapy among patients with non-small lung cancer and PD-L1 expressions of <1% and 1%-49%.

Transcript: 

Hi, I'm Hossein Borghaei, I’m a medical oncologist at Fox Chase Cancer Center and I see patients with thoracic malignancies. I am here at the Great Debates & Updates in Lung Cancer 2023.

We had a debate regarding how to best treat patients with a diagnosis of non-small cell lung cancer without molecular drivers, who also have PD-L1 expression less than 1%, essentially the negative PD-L1 patient population. This is roughly 30% of our patients that we see in our clinics, both histologies: adenocarcinoma and squamous cell histology. It's a particularly difficult patient population because although the studies clearly indicate that the addition of a checkpoint inhibitor to chemotherapy can be effective in this patient population, the responses and the durability of response is a little bit less than we see in patients that have PD-L1 expressions over 1%, and I think that's been pretty consistent across many different studies.

In this background, we also have information where the use of 2 immunotherapy drugs, PD-1 or PD-L1 inhibitor plus CTLA-4, and there are a couple of different studies that have looked at different combinations of an [immunotherapy] IO/IO combo. I think the important aspect of all of this is, first of all, we don't have any head-to-head comparison saying chemo-IO versus a double-IO with or without chemo is more effective. I think a lot of us are basically looking at the data, doing cross-trial comparisons, and trying to decide what is the best treatment options. But what I argued for was that, at least in my experience, an IO/IO combination for tumors, particularly squamous or histology without PD-L1 expression, gives me a better durability of response and more of that what we call the tail of the curve survival in that patient population. My argument was an IO/IO combination would be a more appropriate way, again, realizing that we're probably not going to have head-to-head comparisons in this area and that long-term survival in the tail of the curve becomes a little bit more important.

We also debated whether the addition of 2 cycles of chemotherapy, as we have in CheckMate 9LA, is meaningful. I think definitely the 2 cycles of chemotherapy avoids having that rapid progression in the beginning, but I doubt that it's doing anything with that long- term survival of these patients.

At the end of the day, I think what we can all agree on is that we don't have a specific biomarker beyond PD-L1 to help us figure out who should get what kind of treatment and I think that is going to unfortunately be with us until we find a better way of selecting patients. Same argument was used for PD-L1 between 1% and 49%, and I think there was more of an agreement among all of us that the chemo plus the checkpoint inhibitor does seem to be a better treatment option for that particular group of patients, again, until we get additional information and figure out what else we can do.

Source:

Borghaei, H. Debate: How to Handle PD-L1 <1% - IO Combos. Presented at Great Debates & Updates in Lung Cancer; September 21-23; New York, NY.

Borghaei, H. Debate: How to Handle PD-L1 1-49% - IO Only. Presented at Great Debates & Updates in Lung Cancer; September 21-23; New York, NY.