Cemiplimab Continues to Show Benefit Vs Chemo in PD-L1 ≥50% NSCLC

A long-term follow-up of the phase 3 EMPOWER-Lung 1 found cemiplimab exhibited continued benefit in patients with NSCLC who have a PD-L1 expression of 50% or more.

Cemiplimab-rwlc (Libtayo) continued to show long-term, durable clinical benefits when compared with chemotherapy in the first-line treatment of patients with advanced non–small cell lung cancer (NSCLC) with PD-L1 expression in 50% or more of tumor cells, according to 5-year follow-up results from the phase 3 EMPOWER-Lung 1 trial (NCT03088540) published in the Journal of Thoracic Oncology.1

With a median follow-up for the total study population was 59.6 months (IQR, 55.1-66.7). The median overall survival (OS) was 26.1 months (95% CI, 22.1-31.9) with cemiplimab vs 13.3 months (95% CI, 10.5-16.2) with chemotherapy (HR, 0.59; 95% CI, 0.48-0.72; P <.0001) in patients with PD-L1 of 50% or more; the median progression-free survival (PFS) was 8.1 months (95% CI, 6.2-8.8) vs 5.3 months (95% CI, 4.3-6.1), respectively (HR, 0. 50; 95% CI, 0.41-0.61; P <.0001). The overall response rate (ORR) per the independent review committee was 46.5% (95% CI, 40.6%-52.5%) vs 20.6% (95% CI, 16.1%-25.8%), respectively (OR, 3.34; P <.0001); the median duration of response (DOR) was 24.1 months (95% CI, 16.8-33.2) vs 5.9 months (95% CI, 4.3-6.4).

In the intention-to-treat population, the median OS was 23.4 months (95% CI, 19.4-27.6) with cemiplimab vs 13.7 months (95% CI, 11.2-16.2) with chemotherapy (HR, 0.64; 95% CI, 0.54-0.77; P <.0001); the median PFS was 6.3 months (95% CI, 4.6-8.3) vs 5.2 months (95% CI, 4.3-6.0), respectively (HR, 0.53; 95% CI, 0.46-0.66; P <.0001). The ORR was 42.3% (95% CI, 37.1%-47.6%) vs 21.1% (95% CI, 17.0%-25.7%), respectively (OR, 2.74; P <.0001); the median DOR was 24.1 months (95% CI, 18.6-35.2) vs 5.5 months (95% CI, 4.3-6.3).

Across all PD-L1 expression level subgroups (50%-60%, more than 60%-less than 90%, and 90% or greater), cemiplimab demonstrated OS benefits whereas chemotherapy subgroups demonstrated similar OS benefits across all PD-L1 levels. In patients with PD-L1 expression greater than 90%, the median OS was 38.8 months (95% CI, 22.9-not evaluable) compared with 13.7 months (95% CI, 8.8-20.6) with chemotherapy; the median PFS was 14.7 months (95% CI, 10.2-21.1) vs 5.1 months (95% CI, 4.2-6.2). The ORR was 60.6% (95% CI, 50.3%-70.3%) vs 17.9% (95% CI, 10.8%-27.1%).

Of the patients with PD-L1 expression 50% or more, patients with squamous histology who received cemiplimab (n = 123) had a median OS of 22.7 months (95% CI, 17.3-31.5) vs 13.5 months (95% CI, 10.0-16.2) in those with squamous histology who received chemotherapy (n = 122; HR, 0.51; 95% CI, 0.38-0.69); median PFS was 8.3 months (95% CI, 5.6-9.4) vs 5.9 months (95% CI, 4.5-6.2), respectively (HR, 0.44; 95% CI, 0.32-0.60). In the non-squamous subgroup, the median OS was 28.7 months (95% CI, 22.9-44.3) vs 13.0 months (95% CI, 9.7-19.4), respectively (HR, 0.664; 95% CI, 0.502-0.878; P = .0038); the median PFS was 6.5 months (95% CI, 4.4-12.4) vs 4.9 months (95% CI, 4.1-6.1), respectively (HR, 0.55; 95% CI, 0.42-0.72; P <.0001).

“Our results also demonstrated that cemiplimab benefits increased with PD-L1 expression levels, with the PD-L1 ≥90% group notably deriving the largest clinical benefits,” stated study author Saadettin Kilickap, MD, professor at Istinye University Faculty of Medicine in the Department of Medical Oncology at Liv Hospital in Turkey.1 “These long-term data continue to support the use of cemiplimab as a first-line therapy in patients with advanced NSCLC with PD-L1 ≥50%.”

A total of 712 patients were included in the trial and randomly assigned, in a 1:1 ratio, to receive either 350 mg of intravenous cemiplimab every 3 weeks for 2 years (n = 357) or investigator’s choice of chemotherapy (n = 355).

Eligible patients were 18 years or older with histologically or cytologically confirmed stage IIIB, IIIC, or IV squamous or non–squamous advanced untreated NSCLC with PD-L1 expression 50% or more. Additionally, patients had an ECOG performance status of 0 or 1, at least 3 months of life expectancy, and adequate organ and bone marrow function. Those who never smoked or who had EGFR, ALK, or ROS1 mutations were ineligible for enrollment.

The primary trial end points were OS and PFS. Secondary end points included ORR, DOR, patient-reported outcomes, safety, and tolerability.

Previously, the primary analysis and 3-year follow-up were reported. This analysis was pre-specified by the protocol due to the occurrence of 476 survival events.2,3

No new safety signals were identified since the previously reported analyses. Duration of exposure to cemiplimab was 36 weeks (IQR, 13.9-93.0), and to chemotherapy was 18 weeks (IQR, 11.7-20.1).

Treatment-related adverse events (TRAEs) of grade 3 or higher were observed in 18.3% of patients with cemiplimab and 39.9% with chemotherapy. TRAEs led to discontinuation in 4.2% and 2.9%, respectively, and death in 2.8% and 2.0%. Since the 3-year follow-up, no new deaths associated with TRAEs or immune-related deaths occurred.

In February 2021, results from the EMPOWER-Lung 1 trial led to the FDA’s approval of cemiplimab in first-line locally advanced or metastatic NSCLC with 50% or more PD-L1 expression.4

Reference

1. Kilickap S, Baramidze A, Sezer A, et al. Cemiplimab monotherapy for first-line treatment of patients with advanced NSCLC with PD-L1 expression ≥50%: 5-year outcomes of EMPOWER-lung 1. J Thorac Oncol. Published online March 19, 2025. doi:10.1016/j.jtho.2025.03.033
2. Sezer A, Kilickap S, Gümüş M, et al. Cemiplimab monotherapy for first-line treatment of advanced non-small-cell lung cancer with PD-L1 of at least 50%: a multicentre, open-label, global, phase 3, randomised, controlled trial. Lancet. 2021;397(10274):592-604. doi:10.1016/S0140-6736(21)00228-2
3. Özgüroğlu M, Kilickap S, Sezer A, et al. First-line cemiplimab monotherapy and continued cemiplimab beyond progression plus chemotherapy for advanced non-small-cell lung cancer with PD-L1 50% or more (EMPOWER-Lung 1): 35-month follow-up from a mutlicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2023;24(9):989-1001. doi:10.1016/S1470-2045(23)00329-7. Published correction appears in Lancet Oncol. 2023 Oct;24(10):e405. doi: 10.1016/S1470-2045(23)00463-1
4. FDA approves Libtayo (cemiplimab-rwlc) monotherapy for patients with first-line advanced non-small cell lung cancer with PD-L1 expression of ≥50%. News release. Regeneron Pharmaceuticals, Inc. February 22, 2021. Accessed April 14, 2025. https://tinyurl.com/mr4bbu5h