Continued Cemiplimab Beyond Progression with Addition of Chemotherapy in Patients with Advanced NSCLC with PD-L1 Expression of 50% or Higher: 5-Year Follow-Up from EMPOWER-Lung 1

Introduction: Treatment options are limited for patients with advanced NSCLC who progress on anti–programmed cell death-ligand 1 (anti–PD-L1) monotherapy. Second-line platinum-based chemotherapy provides a short progression-free survival (PFS) of approximately 3 to 4 months. The EMPOWER-Lung 1 study allowed continued cemiplimab with the addition of platinum-based chemotherapy after progression as a second-line treatment (cemiplimab beyond progression [CBP]). Here, we report long-term outcomes in this setting. Methods: Patients (N = 712) with advanced NSCLC were randomized 1:1 to cemiplimab or histology-appropriate chemotherapy. This exploratory analysis evaluated efficacy and safety in the CBP setting in 73 patients (of 357 in the cemiplimab arm) who had at least one scan after progression on cemiplimab and received at least one dose of chemotherapy plus cemiplimab. Responses were assessed by an independent review committee against a new baseline, defined as the last scan before the initial dose of chemotherapy. Results: In the CBP setting, the objective response rate was 27.4%, the median duration of response was 11.5 months (95% confidence interval: 6.0–19.3), and median PFS was 6.4 months (95% confidence interval: 6.1–9.1). Median overall survival from the time of randomization was 27.4 months (including 15.1 mo after the addition of chemotherapy). CBP treatment benefit was observed irrespective of histology, PD-L1 levels, or response to initial first-line cemiplimab monotherapy. Grade 3 or higher treatment-emergent adverse events occurred in 35.6% of patients, and immune-mediated adverse events occurred in 2.7% of patients. Conclusions: This exploratory analysis revealed the clinical benefit of continuing cemiplimab after progression with the addition of chemotherapy, without new safety signals.