First-line cemiplimab improves survival in unresectable NSCLC

First-line treatment with cemiplimab, either as monotherapy or in combination with platinum-based chemotherapy, provides clinical benefits to patients with unresectable locally advanced nonsmall cell lung cancer (NSCLC) who are not candidates for definitive concurrent chemoradiation, as shown by long-term follow-up data from EMPOWER-Lung studies.

“Our data highlight that cemiplimab addresses an unmet clinical need for patients with unresectable locally advanced NSCLC who are not candidates for concurrent chemoradiation,” said lead researcher Ewa Kalinka from the Polish Mother’s Memorial Hospital Research Institute in Łódź, Poland, who presented these findings at the recent ELCC 2023 in Copenhagen, Denmark.

In this subanalysis of EMPOWER-Lung 1 and EMPOWER-Lung 3 studies, Kalinka and colleagues assessed patients with squamous or nonsquamous NSCLC that was metastatic or locally advanced (not suitable for definitive concurrent chemoradiation) without EGFR, ALK, or ROS1 genomic aberrations.

In the EMPOWER-Lung 1 trial, patients were randomly assigned to either first-line cemiplimab monotherapy or chemotherapy for NSCLC with ≥50-percent programmed cell-death-ligand (PD-L1) expression. In the EMPOWER-Lung 3 study, participants were randomized to either first-line cemiplimab plus chemotherapy or placebo plus chemotherapy, irrespective of PD-L1 expression level.

Fifteen percent of patients in each trial received treatment for locally advanced NSCLC.

In EMPOWER-Lung 1, first-line cemiplimab monotherapy resulted in a median overall survival (OS) of 26.1 months compared with 13.9 months with chemotherapy (hazard ratio [HR], 0.67, 95 percent confidence interval [CI], 0.38‒1.17; p=0.1532) at 3-year follow-up. Progression-free survival (PFS) was 8.1 vs 6.2 months (HR, 0.56, 95 percent CI, 0.34‒0.95; p=0.0286). [ELCC 2023, abstract 114M0]

Additionally, the objective response rate (ORR) was 49 percent with monotherapy relative to 31 percent in the combination therapy. The median duration of response was 18.8 vs 6.2 months, respectively.

In the other EMPOWER trial, patients with locally advanced NSCLC enjoyed greater clinical benefits with first-line cemiplimab plus chemotherapy than with placebo plus chemotherapy at 2-year follow-up. The median OS was 24.1 vs 13.8 months (HR, 0.50, 95 percent CI, 0.27‒0.95; p=0.0293), while the median PFS was 12.5 vs 6.2 months (HR, 0.34, 95 percent CI, 0.19‒0.61; p=0.0002).

In addition, the ORR was 58 percent with cemiplimab plus chemotherapy compared to 29 percent with placebo plus chemotherapy, while the median median duration of response was 27.8 vs 4.2 months, respectively.

“Long-term follow-up data from EMPOWER-Lung 1 and EMPOWER-Lung 3 continues to demonstrate the clinical benefits of first-line cemiplimab as monotherapy or in combination with platinum-based chemotherapy for the treatment of patients with locally advanced NSCLC,” the researchers said.

Both the EMPOWER-Lung 1 and EMPOWER-Lung 3 studies applied broad inclusion criteria and enrolled patients with unresectable locally advanced NSCLC who were not candidates for concurrent chemoradiotherapy. [Lancet 2021;397:592-604; Nat Med 2022;28:2374-2380]

“[Such patients] have often been excluded from immunotherapy trials, and their care represents an unmet medical need,” the researchers said.