Follow-up data from Part 2 of the Phase III EMPOWER-Lung 3 trial continues to demonstrate the clinical benefits of cemiplimab in combination with chemotherapy versus chemotherapy alone among patients with advanced squamous and non-squamous non-small cell lung cancer (NSCLC), across PD-L1 levels. These findings were presented during the 2023 European Lung Cancer Congress (Abstract 50) and published in the Journal of Thoracic Oncology (2023; doi: 10.1016/j.jtho.2023.03.008).
"EMPOWER-Lung 3 (NCT03409614) is a double-blind, placebo-controlled, Phase III study evaluating first-line cemiplimab plus platinum-based chemotherapy versus chemotherapy alone for the treatment of patients with advanced NSCLC, irrespective of PD-L1 expression or histology," noted lead study author Tamta Makharadze, MD, clinical oncologist at LTD High Technology Hospital Medical Center in Batumi, Georgia.
The FDA approved cemiplimab plus platinum-based chemotherapy in November 2022 for the treatment of advanced non-small cell lung cancer in adults with EGFR, ALK, or ROS1 aberrations. This approval was supported by earlier data from the EMPOWER-Lung 3 trial.
The primary analysis of the study, after 16.4 months of follow-up, demonstrated clinically meaningful and statistically significant improvements in overall survival, progression-free survival, objective response rate, and duration of response among patients treated with the combination versus chemotherapy alone, according to Makharadze, who presented the protocol specified final overall survival analysis during ELCC.
Key Takeaways
The study authors randomized patients 2:1 to receive 4 cycles of platinum-doublet chemotherapy combined with 350 mg cemiplimab (n=312) or placebo (n=154) every 3 weeks for up to 108 weeks. Eligible patients met the following criteria: treatment-naive advanced NSCLC (non-squamous and squamous histology; Stage IIIb/IV); any PD-L1 expression; no EGFR, ALK, or ROS1 aberrations; and ECOG performance status 0 or 1. Treated, clinically stable CNS metastases were also allowed.
Overall survival was the primary endpoint. Key secondary endpoints included progression-free survival (PFS) and objective response rate (ORR). After a median follow-up of 28.4 months, Makharadze and colleagues found that cemiplimab in combination with chemotherapy continued to demonstrate significantly improved overall and PFS compared with chemotherapy alone. Data showed a median overall survival of 21.1 months among patients treated with cemiplimab plus chemotherapy compared with 12.9 months for individuals who received chemotherapy alone.
Cemiplimab plus chemotherapy also led to improved progression-free survival versus chemotherapy alone at 8.2 months and 5.5 months, respectively. Makharadze reported an objective response rate of 43.6 percent for the combination arm and 22.1 percent for the chemotherapy-only group. Duration of response was 16.4 and 7.3 months, respectively.
An exploratory analysis supported the clinical benefit of cemiplimab in combination with chemotherapy in both squamous and non-squamous histologies. Among patients with squamous disease, Makharadze noted that the median overall survival with cemiplimab plus chemotherapy was 22.3 months versus 13.8 months with chemotherapy alone. The median PFS in this group was 8.2 months and 4.9 months, respectively.
Among patients with non-squamous disease, the median overall survival for the cemiplimab combination and chemotherapy-only arms was 19.4 months and 12.4 months, respectively. The study authors observed a median PRS of 7.9 months for patients treated with cemiplimab plus chemotherapy compared with 5.7 months in those who only received chemotherapy.
The study authors also performed an exploratory analysis examining efficacy according to PD-L1 expression level, and Makharadze noted during her presentation that "all data favored the cemiplimab plus chemotherapy arm except the overall survival data for patients with less than 1 percent PD-L1 expression. "However, when we are seeing the PFS and ORR data, which are a more proximal and prominent measure of drug efficacy, all data favor cemiplimab plus chemotherapy-even data for patients with a less than 1 percent PD-L1 expression level," she said.
Study authors found that the safety profiles for longer-term use of cemiplimab in combination with chemotherapy were generally consistent with previously reported data. Grade >=3 treatment-emergent adverse events occurred in 48.7 percent of patients who received cemiplimab plus chemotherapy and among 32.7 percent of individuals who were given chemotherapy alone.
This trial was also supported by patient-reported outcomes, according to Makharadze, who noted that "pain was clinically decreased in the group [treated with] cemiplimab plus chemotherapy. These data indicated that cemiplimab plus chemotherapy did not impose toxicity that significantly interfered with quality of life of patients with non-small cell lung cancer."
At 28.4 months, the EMPOWER-3 Lung trial continues to demonstrate an improvement in the benefits associated with cemiplimab plus chemotherapy versus chemotherapy alone in patients with advanced squamous and non-squamous NSCLC, regardless of PD-L1 expression level and without EGFR, ALK, or ROS1 aberrations, the study authors stated.
Summarizing their findings, Makharadze noted, "Longer-term follow-up of patients with advanced non-small cell lung cancer demonstrated that first-line cemiplimab plus chemotherapy continued to show clinically meaningful and statistically significant improvement versus chemotherapy alone.
"Cemiplimab plus chemotherapy also continued to show an acceptable safety profile compared to chemotherapy alone. This finding is supported by favorable patient-reported outcomes and the safety profile is generally consistent with primary analysis," she noted. "This data support the use of cemiplimab plus chemotherapy as first-line treatment for patients with advanced non-small cell lung cancer across histologies and PD-L1 expression rate."
Catlin Nalley is a contributing writer.