Dr Erin Gillaspie Explains the Role of Immunotherapies in Lung Cancer Treatment

Erin Gillaspie, MD, MPH, FACS, of Vanderbilt University Medical Center (VUMC), explained the roles of different immunotherapies in treating lung cancer. Gillaspie is a faculty member of VUMC’s Department of Thoracic Surgery and an assistant professor of thoracic surgery. She also presented at The American Journal of Managed Care^®’s Institute for Value-Based Medicine^® held in Nashville, Tennessee, on August 17, 2023.

Transcript

What is the role of immunotherapies in treating lung cancer and when are they being used?

It's such a timely question because actually this is a hot new therapy in the last decade, and we're actually seeing it applied in a lot more places, which is really, really exciting for us.

Immunotherapy (IO) is sort of a brilliant therapy in that it's helping to leverage our immune system to attack the cancer. Now, when it was first developed, the principal application for it was in the metastatic setting, so people who had disease that had spread to other locations. As they started to do studies using immunotherapy, either as a single agent, so on its own, or combining it with chemotherapies, we're starting to see outcomes coming out in these metastatic trials showing that patients are having an improved or enhanced progression-free survival, so meaning their cancer is either responding and shrinking, or it's keeping them at the same place and sort of avoiding that progression or spread to new and other locations.

With that in mind, and seeing some of those benefits in the later stages, with all of us really wanting the outcomes to be phenomenal in the early stage, none of us want to stop until we're having greater than 90% for all of our stages at 5 years, we start to see some of those therapies trickle into the earlier stage.

The first trial that was approved to move immunotherapy into an earlier stage of lung cancer was the IMpower010 trial. What that trial did is it randomized patients who had completely resected lung cancer. They included stages 1B all the way through 3A. A lot of the analyses were done specifically on that 2 and 3A population.

After the complete resection, they underwent the standard of care chemotherapy, and then they were randomized to either immunotherapy or best supportive care. When we look at the disease-free survival, so we're using a lot of surrogate end points to try and help us understand the efficacy of these therapies with the idea that we want to try to get them to market to our patients faster, disease-free survival statistically significantly better in the immunotherapy arm for patients who are PD-L1 positive in that kind of 2 and 3A arm.

Now, we're starting to get some of the data for the overall survival, and those curves are narrowing just a little bit. Our overall survival isn't significant for that entire population, but when we start to glance at some of the subset analyses, there's some signals that we're seeing. So, perhaps the more advanced stages, so stage 3A and those that are PD-L1 high, so greater than 50%, that kind of median survival still hasn't reached. We have a beautiful separation of the curves, our hazard ratio right now looks like it's going to be statistically significant, but we still don't have quite enough data to make all the conclusions on that.

Based on some of the progression-free survival data, we do see that is an approved regimen, so it is FDA approved, we are seeing it being applied to patients. I think we're still going to need to hone in just a little bit for whom it's going to have the most benefit. All of us are suspecting it's going to be those slightly higher stages, higher PD-L1, but there's no doubt that this is providing a survival benefit to some of our patients in the earlier setting.

Within the neoadjuvant space, we have a lot of excitement as well. CheckMate 816 is really the first of its kind in the neoadjuvant setting using chemo-IO combination prior to surgery. They did some preliminary study, so it's our CheckMate 159, to prove safety of moving immunotherapy into that neoadjuvant space.

This was sort of the second part of that, really using our treatment regimens once we've established safety, so this is our follow-up trial. Patients receive chemotherapy or chemotherapy/immunotherapy for 3 cycles followed by restaging and then surgery. After surgery, treatment was left up to the discretion of the treating physician.

A couple key principal end points for that trial, 1 was pathologic complete response, which was achieved in 24% of the patients with a chemo-IO arm vs 2.2% for the chemo alone. We know looking at both of those groups of patients, so both chemo or chemo-IO, who achieved the pathCR [pathologic complete response], that portends benefit when we're looking at things like disease-free survival and overall survival. That's a great signal for us that we're getting that level of pathologic complete response.

Progression-free survival, or disease-free survival, specific to this study: again, we have this beautiful separation of curves. Still very, very immature overall survival data, however, based on the pathologic complete response and the disease-free survival data, we do have a specific approved regimen as well, and we're seeing a huge amount of uptake for it.

One of the things that I think was really lovely that they did in this trial is they actually collected a lot of surgical end points, and I think that's really important. Anytime we move something into the neoadjuvant space, we want to know that we can deliver it safely to the patients, that we're not having a significant number of people who aren't going on to have that definitive local therapy, and we want to make sure that the surgery can be delivered safely. They were able to show that we're having a high rate of completion of safe surgery, no increased morbidity, no significantly increased time.

We see some trends towards a higher number of cases being able to be performed minimally invasively, higher number of cases of a lesser resection, so more lobectomy, more sleeve resections, fewer pneumonectomies. A lot more data needs to be collected in this space, but really, really, really exciting start.

Now, what do we do in the adjuvant space when we think about something like Checkmate 816? They didn't have a dedicated adjuvant regimen. It was left up to really the discretion of the treating physician who's taking care of this patient. We don't have that quite as teased out, but we have 2 trials coming down the pipeline that I think should help to answer that a little bit better for us, and that's the KEYNOTE-671 and the AEGEAN trials, both of which incorporated that chemo-IO in the upfront compared to chemo alone, and then they have a dedicated and guaranteed immunotherapy arm to follow.

I think that'll help us to understand a little bit better, which of our patients do we need to consider extra therapy in? Is there a certain amount of pathologic residual disease? Do we need to be thinking about some other pieces to help direct and guide that therapy?

It's a very, very exciting time as we see all of these therapies moving into earlier stages. To me, the most exciting part is this tells me that we're going to have great options for our patients in the future. For those of us taking care of the very early stages, there's nothing more frustrating than a trial coming out showing that we still have 35% recurrence for patients with tumors 2 centimeters and less. There's a biologic component to this that we really need more understanding of to make sure we're getting patients the right therapies.