Cemiplimab Monotherapy Induces Durable OS, PFS Benefits in PD-L1+ NSCLC With Brain Metastases

Saadettin Kılıçkap, MD

Frontline cemiplimab-rwlc (Libtayo) plus chemotherapy improved overall survival (OS) and progression-free survival (PFS) compared with investigator’s choice of chemotherapy for patients with PD-L1–positive non–small cell lung cancer (NSCLC) that has metastasized to the brain, according to a long-term exploratory analysis from the international phase 3 EMPOWER-Lung 1 trial (NCT03088540).¹

At a median follow-up of 33.3 months (range, 24.0-50.3), the median OS was not evaluable (NE; 95% CI, 20.6-NE) in the cemiplimab arm vs 20.7 months (95% CI, 9.1-29.9) with chemotherapy alone (HR, 0.42; 95% CI, 0.20-0.87; P = .0168). The 24-month OS rate was 65.9% vs 44.7% in favor of cemiplimab.

The median PFS was 12.5 months (95% CI, 6.1-33.5) vs 5.3 months (95% CI, 2.2-6.5) in favor of cemiplimab (HR, 0.34; 95% CI, 0.18-0.63; P = .0004). The 24-month PFS rate was 39.8% vs NE, again in favor of cemiplimab.

“Cemiplimab showed durable clinical benefits and an acceptable safety profile in [patients with] advanced NSCLC with PD-L1 expression of 50% or more and clinically stable brain metastases at baseline,” said Saadettin Kılıçkap, MD, with the Istinye University Faculty of Medicine in Istanbul, Turkey. He presented the findings during the 2023 European Lung Cancer Congress. “This exploratory analysis of EMPOWER-Lung 1 is one of the largest performed in [patients with] clinically stable brain metastasis with PD-1 monotherapy in a phase 3 clinical trial.”

In EMPOWER-Lung 1, investigators assigned patients to 350 mg cemiplimab every 3 weeks for 108 weeks or until progression or 4 to 6 cycles of investigator’s choice of platinum-based doublet chemotherapy. At progression, patients were allowed to add chemotherapy to cemiplimab treatment.²

Eligible adults had stage IIIB, IIIC, or IV squamous or nonsquamous NSCLC that expressed PD-L1 in at least 50% of tumor cells and an ECOG performance score of 0 or 1.² The full study includes 565 patients; these data come from an analysis of 34 patients in the experimental arm and 35 in the control arm diagnosed with brain metastases at baseline.

The median patient age was 61.0 years (range, 45-77) and 69.6% of the population was younger than 65 years. Men made up 89.9% of the population and White patients made up 79.7%. Asian patients made up 17.4% of the population and 2.9% of patients were American Indian or native Alaskans.

Fifty-three (76.8%) patients had an ECOG score of 1. Most patients (79.7%) had nonsquamous histology while 20.3% had squamous disease. Fifty (72.5%) of patients were former smokers while 19 (27.5%) were current smokers. Never smokers were not eligible.

Tumor response was significantly stronger in the experimental arm (55.9% vs 11.4%; odds ratio, 9.27; 95% CI, 2.62-32.74; P = .0002). The complete response rate was 11.8% with cemiplimab vs 0% with chemotherapy. Median duration of response was 31.7 months (95% CI, 14.7-NE) vs 12.5 months (95% CI, 4.4-NE) in favor of cemiplimab.

Five (14.7%) patients in the cemiplimab arm experienced disease progression in the brain compared with 7 (20.0%) in the chemotherapy arm. Three (8.8%) patients in the experimental cohort had progression due to new lesions and 5 (14.7%) had progression from an existing lesion compared with 5 (14.3%) and 3 (8.6%), respectively, in the chemotherapy cohort.

In both arms, the rate of any grade treatment-emergent adverse effects (TEAEs) was 97.1%. In the experimental arm, 35.3% of patients experienced grade 3 or higher TEAEs and 8.8% required discontinuation due to TEAEs. There were no deaths from TEAEs in this cohort.

In the chemotherapy arm, 60.0% of patients experienced grade 3 or higher TEAEs and 1 (2.9%) patient required discontinuation due to TEAEs. There were 3 (8.6%) deaths from TEAEs in this cohort.

Investigators published 3-year OS findings from EMPOWER-Lung 1 in November 2022. Among patients with PD-L1 expression of at least 50%, the median OS in cemiplimab/chemotherapy arm was 21.9 months (95% CI, 15.5-NE) vs 13.0 months (95% CI, 11.9-16.1) in the chemotherapy alone arm (HR, 0.71; 95% CI, 0.53-0.93; P = .014).³

References

1. Kılıçkap S, ÖzgüroğluM, Sezer A, et al. EMPOWER-Lung 1: Cemiplimab (CEMI) monotherapy as first-line (1L) treatment of patients (pts) with brain metastases from advanced non-small cell lung cancer (aNSCLC) with programmed cell death-ligand 1 (PD-L1) ≥50%: 3-year update. Presented at: 2023 European Lung Cancer Congress; March 29-April 1, 2023; Copenhagen, Denmark. Abstract 10MO.
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. Gogishvili M, Melkadze T, Makharadze T, et al. Cemiplimab plus chemotherapy versus chemotherapy alone in non-small cell lung cancer: a randomized, controlled, double-blind phase 3 trial. Nat Med. 2022;28(11):2374-2380. doi:10.1038/s41591-022-01977-y