First-Line Cemiplimab for Locally Advanced NSCLC: Updated Subgroup Analyses From the EMPOWER-Lung 1 and EMPOWER-Lung 3 Trials

TL;DR

This study shows that cemiplimab, as a first-line treatment or combined with chemotherapy, improves survival and reduces side effects in patients with locally advanced lung cancer.

Contribution

The study provides updated long-term results on cemiplimab's efficacy in locally advanced NSCLC patients not eligible for chemoradiation.

Findings

Cemiplimab monotherapy improved overall and progression-free survival compared to chemotherapy.

Cemiplimab plus chemotherapy showed greater survival benefits and fewer severe side effects than chemotherapy alone.

Patient-reported outcomes were better with cemiplimab than with chemotherapy.

Abstract

Patients with unresectable locally advanced NSCLC who are not candidates for concurrent chemoradiation represent an unmet medical need. We report long-term results for this patient subgroup from two phase III trials.

We analyzed data from patients with locally advanced NSCLC in the EMPOWER-Lung 1 (NCT03088540) and EMPOWER-Lung 3 (NCT03409614) studies. In EMPOWER-Lung 1, patients were randomized 1:1 to first-line (1L) cemiplimab monotherapy or chemotherapy with more than or equal to 50% programmed death-ligand 1 expression. In EMPOWER-Lung 3, patients were randomized 2:1 to 1L cemiplimab plus chemotherapy or chemotherapy, regardless of programmed death-ligand 1 expression.

Patients with locally advanced NSCLC constituted 15% of the overall study populations. With cemiplimab monotherapy, the overall survival (OS) was improved versus chemotherapy (median 26.1 versus 13.9 mo; hazard ratio [HR]: 0.67, 95% confidence interval [CI]: 0.38–1.17) and progression-free survival (8.1 versus 6.2 mo; HR: 0.56, 95% CI: 0.34–0.95). With cemiplimab plus chemotherapy, the OS was improved versus chemotherapy alone (24.1 versus 13.8 mo; HR: 0.50, 95% CI: 0.27–0.95) and progression-free survival (12.5 versus 6.2 mo; HR: 0.34, 95% CI: 0.19–0.61). Treatment-emergent adverse events grade more than or equal to 3 occurred in 37.8% (cemiplimab) and 53.7% (chemotherapy) in EMPOWER-Lung 1 and in 46.7% (cemiplimab plus chemotherapy) and 25.0% (chemotherapy) in EMPOWER-Lung 3. Favorable patient-reported outcomes were observed with cemiplimab monotherapy than chemotherapy; no significant patient-reported outcomes favoring chemotherapy were observed in either study.

This subgroup analysis supports the clinical benefit of 1L cemiplimab as monotherapy or combined with chemotherapy in patients with unresectable locally advanced NSCLC (not candidates for definitive chemoradiotherapy).

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