Cemiplimab 5-Year Data Show Improved Survival in High PD-L1 NSCLC

PD-L1–high non-small cell lung cancer (NSCLC) is a distinct subset where immune checkpoint inhibitors like cemiplimab (Libtayo) demonstrate clinical benefit. Bruna Pellini, MD​, assistant member in the Department of Thoracic Oncology​ at H. Lee Moffitt Cancer Center and Research Institute​ and assistant professor in the Department of Oncology Sciences at the University of South Florida reviewed key findings from the EMPOWER-Lung 1 trial (NCT03088540) during a live Community Case Forum event in St. Louis, Missouri. She discusses the recent 5-year update to the trial findings, which show differences in efficacy by PD-L1 expression and histology.

This article is part 2 of a 2-part series from a Case-Based Roundtable event.

Register today to join a Case-Based Roundtable near you.

CASE UPDATE

A decision was made to initiate cemiplimab monotherapy for this patient.

Targeted Oncology: What is the background of using cemiplimab in a patient with PD-L1–high NSCLC?

Bruna Pellini, MD: There are a lot of IOs that came along later on. During my fellowship at Washington University, these studies were getting published, so the treatment was changing while I was in training. But this one was after my time. The cemiplimab study, EMPOWER-Lung 1, was a global study, and investigators had patients with both squamous and nonsquamous disease.

Because there were a lot of patients outside of the United States in the study, there was a good portion of patients who had squamous cell carcinoma of the lung [approximately 45%]. Not only the patients with stage IV disease were allowed into this trial, but also the patients who were ineligible to get concurrent chemoradiation who had stage IIIB or IIIC [were allowed]. Their PD-L1 expression had to be high. They had to have negative ROS1 fusions, ALK fusions and EGFR mutations, and ECOG performance status had to be 0 or 1. They could enroll if they had stable, treated central nervous system metastases. Also, if they had some symptomatic brain metastases, as long as they were treated, patients were allowed to enroll. This study had a dual primary end point of overall survival [OS] and progression-free survival [PFS].

Cemiplimab was given is every 3 weeks, unlike pembrolizumab [Keytruda], which has every 3 weeks and every 6 weeks infusion schedules. You can do atezolizumab [Tecentriq] every 3 or every 4 weeks. The comparator for EMPOWER-Lung 1 was chemotherapy. One thing that was different in the design of the study comparing to the earlier IO studies like KEYNOTE-024 [NCT02142738] is that at the time of disease progression, the investigators could continue the IO and add the chemotherapy, which was not in the design of IMpower110 [NCT02409342] or KEYNOTE-024 or any of the other IO studies.

What was the updated efficacy seen with cemiplimab in EMPOWER-Lung 1?

When you look at OS at 5 years, there were 29.0% of patients alive who received cemiplimab. I don't like telling median PFS to my patients. I usually say [what percent were alive at] 2 to 5 years, because otherwise they get super attached to the number. In terms of PFS, it was 20.8% at 3 years who were still free of disease progression, which is quite amazing. There was a median PFS of 8.1 months.

One thing I like that they published is the OS by PD-L1 status. This has been something that other groups had analyzed…showing there are differences. Fifty percent expression is very different than 90% expression. This phase 3 global study analysis showed that if a patient had a PD-L1 of 90%, the median OS is close to 39 months, as opposed to approximately 20 months when there is 50% to 60% expression.

Then you may ask the question, what is the ideal cutoff? We don't know; it's an imperfect biomarker. But the way they did the analysis here was 50% to 60%, 61% to 89%, and 90% expression or above. There was a median [OS] of 38.8 months for [patients with PD-L1 expression] over 90%, 26.2 months for 61% to 89%, and 50% to 60% was 19.5 months. This is something to remember when we're making decisions.

When it comes to tumor response, it's nothing different than what we are used to. There was a 46.5% response rate. If you have a patient who has [higher response] to the therapy, you're going to have longer duration of response. So at 3 years, there was 38% of the patients free of disease progression…and a median duration of response close to 2 years.

How does the histology of a patient’s NSCLC affect their survival?

When it comes to histology, in my opinion when analyzing these data, I think this drug works extremely well for squamous cell carcinoma of the lung. It's not just for squamous cell carcinoma of the lung. If you look at the approvals, it was the first one that was approved for cutaneous, metastatic squamous disease, then it came the lung squamous approval. Now they have approval for penile squamous cell carcinoma.

Usually when you separate the squamous and the nonsquamous, of course you're going to see better numbers with nonsquamous in general, because of the biology of the disease, which was seen in this trial. But the fact that you still see a median OS close to 23 months in the squamous group is very good to me. Even the fact that at 5 years, you have 25.5% alive is something interesting. It was 23 months roughly for squamous disease, and 29 months roughly for nonsquamous disease.

The median PFS was 6.5 months for nonsquamous as opposed to 8.3 months for squamous, but usually we expect it to be the opposite. I can only say that this drug is effective in both histologies, but personally, I think it is an extremely good drug for squamous histology.

Was there anything that stood out about cemiplimab’s toxicity?

When it comes to safety profile, I don't think there's anything different when you look at the IOs. I think they're all very similar in terms of adverse events. When it comes to pneumonitis, this drug had 2.5% cases of any-grade pneumonitis, and less than 1% was grade 3 or higher. The other drugs were around 5% to 8%, but these are different populations. It doesn't seem to have higher rates of interstitial lung disease or pneumonitis in the context of all the immune checkpoint inhibitors. There was about 20% of patients who had any-grade hypothyroidism. We see this across the board with IOs. The arthralgia is also a problem, but nothing major. It's similar to what we are used to prescribing.

Register today to join a Case-Based Roundtable near you.

DISCLOSURES: Pellini previously reported honoraria from Foundation Medicine, Merck, and AstraZeneca; a consulting or advisory role with AstraZeneca, Regeneron, Illumina, Bristol Myers Squibb/Roche, Merus, Bayer, Gilead Sciences, Foundation Medicine, and OncoHost; and travel, accommodations, or expenses from Bristol Myers Squibb/Roche and MSD.

REFERENCE:

Kilickap S, Baramidze A, Sezer A, et al. Cemiplimab monotherapy for first-line treatment of patients with advanced NSCLC With PD-L1 expression of 50% or higher: five-year outcomes of EMPOWER-Lung 1. J Thorac Oncol. 2025;20(7):941-954. doi:10.1016/j.jtho.2025.03.033