Research Information System
JTO CLINICAL AND RESEARCH REPORTS, vol.7, no.4, 2026 (ESCI, Scopus)
Introduction: 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. Methods: 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. Results: 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. Conclusions: 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). 2026 The Authors. Published by Elsevier Inc. on behalf of the International Association for the Study of Lung Cancer. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).