Frontline Treatment of PD-L1+ Stage IV NSCLC: Cemiplimab

Roy S. Herbst, MD, PhD, of Yale Cancer Center, highlights treatment advances in stage IV non–small cell lung cancer, including cemiplimab as frontline monotherapy based on EMPOWER-Lung 1.

Mark A. Socinski, MD: Hello, and welcome to this OncLive® Peer Exchange®, “Updates in Immunotherapy for Non–Small Cell Lung Cancer.” I’m Dr Mark Socinski from the AdventHealth Cancer Institute in Orlando, Florida. Joining me in this discussion are five of my colleagues. I’d like them to introduce themselves. I’ll start with Martin.

Martin Dietrich, MD, PhD: Hello, I’m Dr. Martin Dietrich. I’m a medical oncologist at Florida Cancer Specialists & Research Institute at the University of Central Florida Cancer Center in Lake Nona.

Mark A. Socinski, MD: Roy?

Roy S. Herbst, MD, PhD: Hi, I’m Dr. Roy Herbst. I’m the chief of medical oncology and an associate director of translational research at the Yale Cancer Center in New Haven, Connecticut.

Mark A. Socinski, MD: Chaitali?

Chaitali Nangia, MD: Hi. I’m Chaitali Nangia, medical oncologist at Hoag Cancer Center in Newport Beach, California.

Mark A. Socinski, MD: Sticking with California: Sandip?

Sandip P. Patel, MD: Hi, everyone. I’m Sandip Patel. I’m a medical oncologist and an associate professor at the University of California San Diego where I lead our experimental therapeutics program, as well as our clinical trials office.

Mark A. Socinski, MD: And last but not least: Neal?

Neal Edward Ready, MD, PhD: Hi, I’m Neal Ready, a professor of medicine at Duke Medical Center in Durham, North Carolina.

Mark A. Socinski, MD: Thank you all for joining today. Today, we’re going to be discussing a number of topics, including initial immunotherapy-based regimens for metastatic non–small cell lung cancer, consolidation immunotherapy in stage III disease, and perioperative regimens with immunotherapy in resectable non–small cell lung cancer. We’ll discuss the latest research in the field and the impact of recent clinical trials on making decisions around treatment selection. Let’s get started on our first topic.

I’m going to ask Roy to give us an overview of frontline immuno-oncology. Back in October 2016, KEYNOTE-024 led to the approval of pembrolizumab in the high expressers, greater than 50% PD-L1 positive. Since then, we’ve had the addition in this space of both atezolizumab and cemiplimab. I wanted Roy to give us his thoughts and overview of this population and these studies.

Roy S. Herbst, MD, PhD: Thanks, Mark. It’s great to see that results are being reproduced with other agents, and immunotherapy. I guess it’s more than 10 or 11 years that we’ve been using these agents in lung cancer, but really only in the last three or four, or maybe five, that we’ve had approved agents. Immunotherapy is a standard in the frontline therapy. We already had, going into this year, pembrolizumab from KEYNOTE-024 approved in frontline versus chemotherapy, and then atezolizumab beating chemotherapy, that being a PD-L1 inhibitor—pembrolizumab is a PD-1 inhibitor—in the IMpower110.

Now we have the EMPOWER-Lung 1 trial, which is looking at cemiplimab, another PD-1 inhibitor. This trial, as you can imagine, was done pretty much in the rest of world because there were already approved agents for frontline therapy in the United States. It brought access to this drug in a large number of countries. Interestingly, to be in this trial, you had to have PD-L1 greater than 50%, or it’s also for high PD-L1. And you had to have had some smoking history. They also allowed patients with brain metastases, so it was a real-world population. But I was impressed that the hazard ratio was in the 0.5–0.6 range for survival, and with PFS [progression-free survival], the difference was quite significant, as well as response rate. The toxicities of this agent don’t look much different from what’s seen with some of the other immune-acting agents. What does this mean? It means that there’s another agent in the front line that can be used alone in the 50% positive patients or combined with other agents. I expect we’ll see that as well. But I’m reassured that we have three agents like this as single agents in the front line. Of course, we have combos as well, bringing nivolumab and ipilimumab into the fold. it’s good for patients. It gives us more options in the clinic.

Mark A. Socinski, MD: Roy, as you point out, it excluded never-smokers from this trial, which may have enriched it for the squamous histology patients, who were well into the 40% or so. They’ve also included the hepatitis B and C population, at least who have chronic viral infections, although there were very few patients with this issue on the trial. How do you see this influencing choices? In my practice, you’ve been using pembrolizumab for so long. It’s not clear that this is necessarily better. It certainly doesn’t appear to be. It appears to be every bit as safe as pembrolizumab. I’m wondering how you put this into the current landscape.

Roy S. Herbst, MD, PhD: It’s reassuring. It looks about the same at this stage—not so early. It’s a bit more mature than atezolizumab data were when first presented. But of course, from Drs [Julie] Brahmer and [Martin] Reck and team, we have five-year data with KEYNOTE-024. The 5-year survival was 35%. That’s the gold standard. This drug looks, at this point, to be quite similar. Antibodies against PD-1 or PD-L1, this 1 against PD-1, might have slightly different epitopes that they recognize. Perhaps, they have slightly different half-lives. They’re not all the same. So far, this has also beat chemotherapy, a little bit different population.

This gets to preference. I’m used to using pembrolizumab in this setting. I probably still will. Is there a time when my hospital pharmacy officer might say, “Roy, we’ve made a deal, and we’re using this drug, and we feel it’s equivalent”? If that were to happen, 1 could say that probably is true, and we do that. My goal is to get immunotherapy to more patients. Mark, having done this for a long time, these drugs work only if people have access and can afford it. Certainly, having multiple choices are good. But right now, I’m still using pembrolizumab. We just published the KEYNOTE-010 second-line data, and those looks pretty good in the high group—20%, 25% at five years. Let’s keep following these data. I’m sure we’ll see them again at different congresses.

Mark A. Socinski, MD: I want to get your thoughts on one of the issues: crossover rate on the chemotherapy arm. The crossover rate was in excess of 70% to cemiplimab. We still see, even though most patients are getting the immunotherapy second line, that the survival doesn’t catch up to you getting first line. Do you have any thoughts in that area? We saw the same thing with KEYNOTE-024. Dr. Brahmer presented some data along the same lines.

Roy S. Herbst, MD, PhD: Yeah, KEYNOTE-024. I discussed that at ESMO [European Society for Medical Oncology Congress] last year. But even at 66% crossover, and the survival didn’t get up to the 35 months. Maybe it approached 20 months or something like that. My feeling is your best shot with immunotherapy is to get it right away. Certainly, having used chemotherapy for quite some time, you’re never going to cure anyone or have that long-term tail of the curve with chemotherapy. What happens with a crossover is some patients don’t make it through. They progress; they get neutropenic; they have a pneumonia. Something happens during the first therapy. You can’t always rescue those patients. Frontline use of these drugs is where they should be. Of course, we’re seeing, from ASCO [American Society of Clinical Oncology Annual Meeting], adjuvant therapy having effects, so move these drugs earlier and earlier with a stronger, healthier patient. But it’s nice to know that if you don’t give it front line, perhaps you’ve got someone who can’t get immunotherapy for some reason, then you can always add it in later.


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